Functional foods of plant origin

Numerous plant foods or physiologically active ingredients derived from plants have been investigated for their role in disease prevention and health. However, only a small number of these have had substantive clinical documentation of their health benefits. An even smaller number have surpassed the rigorous standard of “significant scientific agreement” required by the FDA for authorization of a health claim, which will be discussed in further detail below. Those plant foods currently eligible to bear an FDA-approved health claim include oat soluble (β-glucan) fiber, soluble fiber from psyllium seed husk, soy protein and sterol- and stanol-ester–fortified margarine.

Some plant-based foods or food constituents currently do not have approved health claims, but have growing clinical research supporting their potential health benefits, and thus would be described as having moderately strong evidence. These include cranberries, garlic, nuts, grapes and chocolate and are discussed briefly below.

Cranberries have been recognized since the 1920s for their efficacy in treating urinary tract infections. A landmark clinical trial confirmed this therapeutic effect in a well-controlled study involving 153 elderly women. More recent research has confirmed that condensed tannins (proanthocyanidins) in cranberry are the biologically active component and prevent E. coli from adhering to the epithelial cells lining the urinary tract. New preliminary research suggests that the antiadhesion properties of the cranberry may also provide other health benefits, including in the oral cavity.

Garlic (Allium sativum) has been used for thousands of years for a wide variety of medicinal purposes; its effects are likely attributable to the presence of numerous physiologically active organosulfur components (e.g., allicin, allylic sulfides). Garlic has been shown to have a modest blood pressure–lowering effect in clinical studies, while a growing body of epidemiologic data suggests an inverse relationship between garlic consumption and certain types of cancer, particularly of the stomach . The latter may be due in part to garlic’s ability to inhibit the activity of Helicobacter pylori (the bacterium that causes ulcers). The best-documented clinical effect of garlic, however, concerns its ability to reduce blood cholesterol. A meta-analysis of 13 placebo-controlled double blind trials indicated that garlic component(s) (10 mg steam distilled oil or 600–900 mg standardized garlic powder) significantly reduced total cholesterol compared with placebo by 4–6%. However, the Agency for Healthcare Research & Quality, which examined randomized, controlled trials at least 1 mo in duration, concluded that, although clinical trials show several promising, modest, short-term effects of garlic supplementation on lipid and antithrombotic factors, “effects on clinical outcomes are not established …” This is likely due to lack of consistency among studies in type of preparation used and overall study design.

Although foods high in fat have traditionally not been regarded as “heart-healthy” (except for fatty fish), evidence is accumulating on the cardiovascular benefits of a variety of nuts, when they are part of a diet that is low in saturated fat and cholesterol. Clinical trials, which have specifically examined the effect of almonds on blood lipids, have found that these tree nuts significantly reduced total cholesterol by 4–12% and LDL cholesterol by 6–15%. More recently, a Life Sciences Research Office review of six clinical intervention trials with walnuts consistently demonstrated decreases in total and LDL cholesterol that should lower the risk of CHD.

In the late 1970s researchers noted that residents in certain areas of France, who were avid drinkers of red wine, had less heart disease than other Western populations even though they consumed more fat in their diet. This observation triggered numerous investigations into this so-called “French Paradox” and subsequent research confirmed the presence of high concentrations of antioxidant polyphenolics in red grape skins. It must be noted however, that moderate consumption of any alcoholic beverage, e.g., beer, wine or distilled spirits, has been shown in a number of studies to reduce the risk of heart disease in selected populations.

For those wishing to abstain from alcohol, recent clinical trials demonstrate that grape juice may also exert beneficial effects similar to those of red wine because both are rich in phenolic antioxidant compounds. Consumption of grape juice has been shown to reduce platelet aggregation. Another food that is a source of polyphenolics and is just beginning to be investigated for its potential benefits to heart health is chocolate. Chocolate contains flavonoids (procyanidins), which may reduce oxidative stress on LDL cholesterol. In a recent clinical trial involving 23 subjects consuming a diet supplemented with chocolate and cocoa powder providing ∼466 mg procyanidins/d, time to oxidation of LDL cholesterol was increased by 8% compared with subjects consuming a normal American diet.

Epidemiologic data are accumulating on the health benefits of several additional functional foods or food components of plant origin, including tea (catechins), lycopene from tomatoes, particularly cooked and/or processed tomato products, and the carotenoids lutein and zeaxanthin from green leafy vegetables.

The effect of green or black tea consumption on cancer risk has been the focus of numerous studies. Studies in animals consistently show that consumption of green tea reduces the risk of various types of cancers. Only a few studies have thus far assessed the effects of black tea. Green tea is particularly abundant in specific polyphenolic components known as catechins. The major catechins in green tea are (−)-epicatechin, (−)-epicatechin-3-gallate, (−)-epigallocatechin and (−)-epigallocatechin-3-gallate (EGCG). One cup (240 mL) of brewed green tea contains up to 200 mg EGCG, the major polyphenolic constituent of green tea.

Although ∼100 epidemiological studies have examined the effect of tea consumption on cancer risk, the data are conflicting. A recent study involving 26,311 residents from three municipalities in northern Japan found no association of green tea consumption with the risk of gastric cancer. Phase I clinical trials are currently ongoing at the MD Anderson Cancer Center (Houston, TX) in collaboration with the Memorial Sloan-Kettering Cancer Center in New York on the safety and efficacy of consuming the equivalent of >10 cups of green tea by 30 cancer patients with advanced solid tumors.

Tomatoes and tomato products are also being investigated for their role in cancer chemoprevention and are unique because they are the most significant dietary source of lycopene, a non-provitamin A carotenoid that is also a potent antioxidant. A comprehensive review of 72 epidemiologic studies found an inverse association between tomato intake or plasma lycopene concentration and the risk of cancer at a defined anatomical site in 57 of the 72 studies reviewed (79%); in 35 of these studies, the inverse associations were statistically significant. No study indicated higher risk with increasing tomato consumption or lycopene blood levels. Further, the risk reduction for about half of all studies reviewed was 40% (i.e., a relative risk estimate of 0.6). Cancers of the prostate, lung and stomach showed the strongest inverse associations, whereas data were suggestive for cancers of the pancreas, colon and rectum, esophagus, oral cavity, breast and cervix.

Most ongoing clinical trials involving lycopene and cancer prevention are focused on prostate cancer, in large part because a 1995 study involving > 47,000 participants from the Health Professionals Follow-Up Study (HPFS) followed from 1986 to 1992 found that >10 servings/wk of tomato sauce, tomatoes, tomato juice or pizza could reduce risk of prostate cancer by 35%; advanced prostate cancer (i.e., more aggressive tumors) was reduced by 53%. More importantly, of the 46 fruits and vegetables evaluated, tomato products were the only foods that were associated with reduced risk of prostate cancer. Additional follow-up data from the HPFS through 1998 further supported the earlier observation that lycopene reduces prostate cancer risk and, more specifically, found that that intake of tomato sauce (2+ servings/wk) was associated with a 23% reduction in prostate cancer risk. The protective effect of tomato products may result from lycopene’s ability to selectively accumulate in the prostate gland, perhaps serving an antioxidant function in that organ. This hypothesis was strengthened by a recent study that found that men with localized prostate adenocarcinoma had significantly reduced prostate DNA oxidative damage after consumption of tomato-sauce based meals containing 30 mg lycopene for 3 wk.

Another carotenoid that has received recent attention for its role in disease risk reduction is lutein, the main pigment in the macula of the eye (an area of the retina responsible for the sharpest vision). More specifically, research is focusing on the role of lutein in eye health due to its ability to neutralize free radicals that can damage the eye and by preventing photooxidation. Thus, individuals who have a diet high in lutein may be less likely to develop age-related macular degeneration (AMD) or cataracts, the two most common causes of vision loss in adults. Because of the increasing evidence for lutein’s role in eye health, supplements that contain this carotenoid are now appearing on the market. There is some concern, however, that lutein in supplement form may not provide the same benefit as the lutein found naturally in foods. In March 2000, the National Eye Institute of the NIH released a statement on lutein and its role in eye disease prevention: “Claims made about an association between lutein and eye health should be approached with caution. The possible benefits of lutein on the eye remain uncertain.” The statement indicates that there is little direct scientific evidence at this time to support a claim that taking supplements containing lutein can decrease the risk of developing AMD or cataract. Nevertheless, the possibility that lutein may reduce the risk of oxidant-related diseases of the eye clearly warrants further research. Good sources of lutein include green leafy vegetables such as spinach (7.4 mg/100 g) and cooked cabbage (14.4 mg/100 g).

Although not yet supported by clinical or epidemiologic data, evidence from in vitro and in vivo (animal) studies supports the cancer-preventive benefits of flaxseed lignans, citrus fruit limonoids  and various cruciferous vegetable phytochemicals, including isothiocyanates and indoles. With respect to the latter, broccoli sprouts are currently being marketed both as a dietary supplement, highlighting the potential cancer-preventive action of one purported physiologically active component, sulforaphane, and as a food containing high levels of sulforaphane. In vitro and in vivo, this component has been shown to be a potent inducer of Phase II detoxifying enzymes in the liver. Such enzymes speed the inactivation of toxic substances and thus accelerate their elimination from the body. The marketing of conventional foods as dietary supplements has engendered controversy, however, as will be discussed below.

GTC Biotherapeutics has successfully engineered goats that excrete 14 varieties of therapeutic protein in their milk. A firm wishing to produce a therapeutic protein in quantity can contract GTC to create transgenic goats that excrete the desired protein in their milk. According to Thomas Newberry of GTC, creating a herd of transgenic goats costs about $100m—expensive, but still only a third the cost of building a protein production facility. Moreover, when a drug maker needs to double production, it simply breeds more animals—thereby avoiding spending $300m on a new factory. Chickens have some advantages over goats or cows. First, chickens lay eggs which, like Tupperware, are sterile, sealed containers for protecting and storing delicate contents. The albumen, or egg white, is an ideal place to store fragile compounds. Second, chickens are quicker to mature and cheaper to breed than goats or cows. A chicken flock can multiply tenfold within a year. And each additional bird requires only one square foot of extra space in a chicken coop. TranXenoGen, an avian transgenics firm based Massachusetts, announced that it had produced two antibodies—one human antibody and one mouse antibody—in the albumens of so-called “chimeric” chickens, which produce the desired protein in some (but not all) their cells. At present, TranXenoGen is aiming to produce transgenic chickens that make eggs containing insulin and human serum albumen, with an eye on getting regulators to stamp their seal of approval on drugs produced this way.