Cruciferous Vegetables and Cancer Risk
Jane Higdon, Ph.D.
What are cruciferous vegetables?
Cruciferous or Brassica vegetables come from plants in the family known to botanists as Cruciferae or alternately, Brassicaceae. Plants in the Cruciferae family have flowers with four equal-sized petals in the shape of a cross. "Brassica" is the latin term for cabbage. Commonly consumed cruciferous vegetables include broccoli, Brussels sprouts, cabbage, cauliflower, collard greens, kale, kohlrabi, mustard, rutabaga, turnips, bok choy, and Chinese cabbage. Arugula, horseradish, radish, wasabi, and watercress are also cruciferous vegetables.
What's so special about cruciferous vegetables?
Like other dark green vegetables, many cruciferous vegetables are rich in folate and chlorophyll. One of the unique things about cruciferous vegetables is that they are rich sources of glucosinolates, sulfur-containing compounds that give them their pungent aromas and spicy (some say bitter) taste. Chopping or chewing cruciferous vegetables releases myrosinase, an enzyme that breaks down glucosinolates into biologically active compounds, such as indoles and isothiocyanates (see figure below).
How might compounds in cruciferous vegetables help protect against cancer?
Folate plays an important role in DNA repair and the methylation of DNA, which affects the expression of cancer-related genes. Chlorophyll can form tight complexes with chemicals from tobacco smoke or charred meat (cooked meat mutagens) that are known or suspected to cause cancer. The tight binding of chlorophyll to these potential carcinogens may interfere with their absorption and reduce the amount that reaches susceptible tissues. Glucosinolate breakdown products, which are unique to cruciferous vegetables, could help prevent cancer in several ways. Isothiocyanates and indoles may increase the activity of enzymes that play an important role in the detoxification and elimination of carcinogens. Indoles may alter the metabolism and activity of estrogens in the body, which could play a role in hormone-associated cancers, such as breast or prostate cancer. Some isothiocyanates, such as sulforaphane, can act as histone deacetylase inhibitors, which have the potential to suppress the development of cancer by turning on tumor suppressor genes in precancerous cells.
Is there any evidence that high intakes of cruciferous vegetables prevent cancer?
Cell culture and small animal studies have found some anticancer effects of substances isolated or derived from cruciferous vegetables. However, some potential risks of supplementation with these substances, such as indole- 3-carbinol, have also been identified (see the article by Susan Tilton).
An extensive review of epidemiologic studies published prior to 1996 reported that the majority (67%) of 87 case-control studies found an inverse association between some type of cruciferous vegetable intake and cancer risk. At that time, the inverse association appeared to be most consistent for cancers of the lung and digestive tract. The results of such retrospective case-control studies are more likely to be distorted by bias in the selection of participants and dietary recall than prospective cohort studies, which collect dietary information from people years before they are diagnosed with cancer. In the past decade, results of prospective cohort studies and studies taking into account individual genetic variation suggest that the relationship between cruciferous vegetable intake and the risk of several types of cancer is more complex than previously thought.
The results of epidemiologic studies of cruciferous vegetable intake and breast cancer risk are inconsistent. Several recent case-control studies in the U.S., Sweden, and China found that measures of cruciferous vegetable intake were significantly lower in women diagnosed with breast cancer than in cancer-free control groups, but cruciferous vegetable intake was not associated with breast cancer risk in a pooled analysis of seven large prospective cohort studies that included more than 350,000 women.
Four out of eight case-control studies published since 1990 found that cruciferous vegetable intake was significantly lower in men diagnosed with prostate cancer than in men in a cancer-free control group. Of the four prospective cohort studies that have examined associations between cruciferous vegetable intake and the risk of prostate cancer, none found statistically significant inverse associations overall. However, the prospective study that included the longest follow-up period and the most cases of prostate cancer found a significant inverse association between cruciferous vegetable intake and the risk of prostate cancer when the analysis was limited to men who had a prostate specific antigen (PSA) test. Since men who have PSA screening are more likely to be diagnosed with early prostate cancer, limiting the analysis in this way reduces detection bias. Presently, epidemiologic studies provide only modest support for the hypothesis that high intakes of cruciferous vegetables reduce prostate cancer risk.
When evaluating the effect of cruciferous vegetable consumption on lung cancer risk, it is important to remember that the benefit of increasing cruciferous vegetable intake is likely to be small compared to the benefit of smoking cessation. Although a number of case-control studies found that people diagnosed with lung cancer had significantly lower intakes of cruciferous vegetables than people in cancer-free control groups, the findings of more recent prospective cohort studies have been mixed. Prospective studies of Dutch men and women, U.S. women, and Finnish men found that higher intakes of cruciferous vegetables (more than three weekly servings) were associated with significant reductions in lung cancer risk, but prospective studies of U.S. men and European men and women found no inverse association.
Although a number of case-control studies conducted prior to 1990 found that people diagnosed with colorectal cancer were more likely to have lower intakes of cruciferous vegetables than people without colorectal cancer, most prospective cohort studies have not found significant inverse associations between cruciferous vegetable intake and the risk of developing colorectal cancer over time. One exception was a prospective study of Dutch men and women, which found that those with the highest intakes of cruciferous vegetables (averaging about 1/2 cup/day) were significantly less likely to develop colon cancer than those with the lowest intakes.
Why can't epidemiologic studies give us a clear answer about the cancer-protective effects of cruciferous vegetables?
Recent research suggests that genetic factors affecting the metabolism of glucosinolate breakdown products may influence the relationship between cruciferous vegetable intake and cancer risk. Glutathione S-transferases (GSTs) are a family of enzymes that metabolize a variety of compounds, including isothiocyanates from cruciferous vegetables, in a way that promotes their elimination from the body. Genetic variations that affect the activity of GSTs have been identified in humans. Specifically, individuals who inherit two copies of the GSTM1-null or GSTT1-null gene cannot produce the corresponding GST enzyme. Lower GST activity in such individuals could result in slower elimination and longer exposure to isothiocyanates after cruciferous vegetable consumption, thus enhancing cancer prevention. In support of this idea, several epidemiologic studies have found that inverse associations between isothiocyanate intake from cruciferous vegetables and the risk of lung cancer or colon cancer were more pronounced in GSTM1-null or GSTT1-null individuals. These findings suggest that the protective effects of high intakes of cruciferous vegetables may be enhanced in individuals who eliminate potentially protective compounds, like isothiocyanates, more slowly. However, low GST activity in smokers may also slow the elimination of tobacco carcinogens. A large case-control study in the U.S. recently found that high intakes of cruciferous vegetables were associated with reduced lung cancer risk only in GSTM1-present individuals, especially current smokers. The complex effects of genediet interactions on cancer risk continue to be an area of active scientific research.
Is there a recommended intake for cruciferous vegetables?
Although many organizations, including the National Cancer Institute, recommend the consumption of 5-9 servings (2 1/2-4 1/2 cups) of fruits and vegetables daily, separate recommendations for cruciferous vegetables have not been established. Much remains to be learned regarding cruciferous vegetable consumption and cancer prevention, but the results of some epidemiologic studies suggest that adults should aim for at least 5 servings (2 1/2 cups) per week of cruciferous vegetables.
Does cooking alter the cancer-protective effects of cruciferous vegetables?
Glucosinolates are water-soluble compounds that may be leached into cooking water. Boiling cruciferous vegetables for 9-15 minutes results in 20-60% decreases in the total glucosinolate content of cruciferous vegetables. Cooking methods that use less water, such as steaming or microwaving, may reduce glucosinolate losses. However, some cooking practices, including boiling, steaming, and microwaving at high power (850-900 watts) may inactivate myrosinase, the enzyme responsible for the breakdown of glucosinolates into isothiocyanates and indoles. Although human intestinal bacteria can break down glucosinolates to some degree, several studies in humans have found that heat inactivation of myrosinase in cruciferous vegetables substantially decreases the bioavailability of isothiocyanates. To maximize the bioavailability of isothiocyanates and indoles, it's probably best to eat cruciferous vegetables raw or microwaved at low power.
Are there cruciferous vegetables that are particularly rich sources of specific isothiocyanates or indoles?
Different cruciferous vegetables contain different profiles of glucosinolates, which result in different profiles of isothiocyanates or indoles when they are chopped or chewed (see table below). For example, broccoli is a rich source of glucoraphanin, the precursor of sulforaphane, and glucobrassicin, the precursor of indole-3-carbinol. Broccoli sprouts are concentrated sources of glucoraphanin, providing 10-100 times more by weight than mature broccoli plants. Broccoli sprouts that are certified to contain at least 73 mg of glucoraphanin (also called sulforaphane glucosinolate or SGS) per 1-oz serving are available in some health food and grocery stores.
Last updated June, 2006