Crucifereos Vegetables

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Linus Pauling InstituteMicronutrient Research for Optimum Health

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Cruciferous Vegetables

Summary

Cruciferous vegetables are unique in that they are rich sources of sulfur-containingcompounds known as glucosinolates. (More Information)

Chopping or chewing cruciferous vegetables results in the formation of bioactiveglucosinolate hydrolysis products, such as isothiocyanates and indole-3-carbinol. (MoreInformation)

High intakes of cruciferous vegetables have been associated with lower risk of lung andcolorectal cancer in some epidemiological studies, but there is evidence that geneticdifferences may influence the effect of cruciferous vegetables on human cancer risk. (MoreInformation)

Although glucosinolate hydrolysis products may alter the metabolism or activity of sexhormones in ways that could inhibit the development of hormone-sensitive cancers,evidence of an inverse association between cruciferous vegetable intake and breast or

prostate cancer in humans is limited and inconsistent. (More Information)

Many organizations, including the National Cancer Institute, recommend eating a variety offruits and vegetables daily; the recommended serving number depends on age, sex, andphysical activity level. However, separate recommendations for cruciferous vegetables havenot been established. (More Information)

Introduction

Cruciferous or Brassica vegetables are so named because they come from plants in the familyknown to botanists as Cruciferae or alternately, Brassicaceae. Many commonly consumedcruciferous vegetables come from the Brassica genus, including broccoli, Brussels sprouts,cabbage, cauliflower, collard greens, kale, kohlrabi, mustard, rutabaga, turnips, bok choy, and

Chinese cabbage (1). Arugula, horse radish, radish, wasabi, and watercress are also cruciferousvegetables.

Cruciferous vegetables are unique in that they are rich sources of glucosinolates, sulfur-containingcompounds that impart a pungent aroma and spicy (some say bitter) taste (2). The hydrolysis(breakdown) of glucosinolates by a class of plant enzymes called myrosinase results in theformation of biologically active compounds, such as indoles and isothiocyanates (3). Myrosinase isphysically separated from glucosinolates in intact plant cells. However, when cruciferous vegetablesare chopped or chewed, myrosinase comes in contact with glucosinolates and catalyzes theirhydrolysis. Scientists are currently interested in the potential for high intakes of cruciferous

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2/21/2012http://lpi.oregonstate.edu/infocenter/foods/cruciferous/


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vegetables as well as several glucosinolate hydrolysis products to prevent cancer (see Indole-3-Carbinol and Isothiocyanates).

Disease Prevention

Cancer

Like most other vegetables, cruciferous vegetables are good sources of a variety of nutrients andphytochemicals that may work synergistically to help prevent cancer (4). One challenge in studyingthe relationships between cruciferous vegetable intake and cancer risk in humans is separating thebenefits of diets that are generally rich in vegetables from those that are specifically rich incruciferous vegetables (5). One characteristic that sets cruciferous vegetables apart from othervegetables is their high glucosinolate content (6). Glucosinolate hydrolysis products could helpprevent cancer by enhancing the elimination ofcarcinogens before they can damage DNA, or byaltering cell-signaling pathways in ways that help prevent normal cells from being transformed intocancerous cells (7). Some glucosinolate hydrolysis products may alter the metabolism or activity ofhormones like estrogen in ways that inhibit the development of hormone-sensitive cancers (8).

An extensive review ofepidemiological 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 (9). At that time, the inverse association appeared to be mostconsistent for cancers of the lung and digestive tract. The results of retrospective case-controlstudies are more likely to be distorted by bias in the selection of participants (cases and controls)and dietary recall than prospective cohort studies, which collect dietary information fromparticipants before they are diagnosed with cancer (10). In the past decade, results of prospectivecohort studies and studies taking into account individual genetic variation suggest that therelationship between cruciferous vegetable intake and the risk of several types of cancer is morecomplex than previously thought.

Lung Cancer

When evaluating the effect of cruciferous vegetable consumption on lung cancer risk, it isimportant to remember that the benefit of increasing cruciferous vegetable intake is likely to besmall compared to the benefit of smoking cessation (11, 12). Although a number ofcase-controlstudies found that people diagnosed with lung cancer had significantly lower intakes of cruciferousvegetables than people in cancer-free control groups (9), the findings of more recent prospectivecohort studies have been mixed. Prospective studies of Dutch men and women (13), U.S. women(14), and Finnish men (15) found that higher intakes of cruciferous vegetables (more than threeweekly servings) were associated with significant reductions in lung cancer risk, but prospectivestudies of U.S. men (14) and European men and women (11) found no inverse association. Theresults of several studies suggest that genetic factors affecting the metabolism of glucosinolatehydrolysis products may influence the effects of cruciferous vegetable consumption on lung cancerrisk (16-21) (see Genetic Influences below).

Colorectal Cancer

A small clinical trial found that the consumption of 250 g/day (9 oz/day) of broccoli and 250 g/dayof Brussels sprouts significantly increased the urinary excretion of a potential carcinogen found inwell-done meat, suggesting that high cruciferous vegetable intakes might decrease colorectalcancer risk by enhancing the elimination of some dietary carcinogens (22). Although a number ofcase-control studies conducted prior to 1990 found that people diagnosed with colorectal cancerwere more likely to have lower intakes of various cruciferous vegetables than people withoutcolorectal cancer (23-26), most prospective cohort studies have not found significant inverseassociations between cruciferous vegetable intake and the risk of developing colorectal cancer overtime (27-32). One exception was a prospective study of Dutch adults, which found that men andwomen with the highest intakes of cruciferous vegetables (averaging 58 g/day) were significantly




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less likely to develop colon cancer than those with the lowest intakes (averaging 11 g/day) (33).Surprisingly, higher intakes of cruciferous vegetables were associated with increased risk of rectalcancer in women in that study. As in lung cancer, the relationship between cruciferous vegetableconsumption and colorectal cancer risk may be complicated by genetic factors. The results ofseveral recent epidemiological studies suggest that the protective effects of cruciferous vegetableconsumption may be influenced by inherited differences in the capacity of individuals to metabolizeand eliminate glucosinolate hydrolysis products (34-37) (see Genetic Influences below).

Breast Cancer

The endogenous estrogen 17beta-estradiol can be irreversibly metabolized to 16alpha-hydroxyestrone (16aOHE1) or 2-hydroxyestrone (2OHE1). In contrast to 2OHE1, 16aOHE1 ishighly estrogenic and has been found to enhance the proliferation of estrogen-sensitive breastcancer cells in culture (38, 39). It has been hypothesized that shifting the metabolism of 17beta-estradiol toward 2OHE1, and away from 16aOHE1, could decrease the risk of estrogen-sensitivecancers like breast cancer (40). In a small clinical trial, increasing cruciferous vegetable intake ofhealthy postmenopausal women for four weeks increased urinary 2OHE1:16aOHE1 ratios,suggesting that high intakes of cruciferous vegetables can shift estrogen metabolism. However, therelationship between urinary 2OHE1:16aOHE1 ratios and breast cancer risk is not clear. Severalsmall case-control studies found that women with breast cancer had lower urinary ratios of

2OHE1:16aOHE1 (41-43), but larger case-control and prospective cohort studies did not findsignificant associations between urinary 2OHE1:16aOHE1 ratios and breast cancer risk (44-46).The results ofepidemiological studies of cruciferous vegetable intake and breast cancer risk arealso inconsistent. Several case-control studies in the U.S., Sweden, and China found that measuresof cruciferous vegetable intake were significantly lower in women diagnosed with breast cancerthan in women in the cancer-free control groups (47-49), but cruciferous vegetable intake was notassociated with breast cancer risk in a pooled analysis of seven large prospective cohort studies(50). In a prospective study in 285,526 women, total vegetable consumption was not related torisk of breast cancer; individual subcategories of vegetable type, including cabbages, rootvegetables, and leafy vegetables, were not individually associated with breast cancer in this cohort(51).

Prostate Cancer

Although glucosinolate hydrolysis products have been found to inhibit growth and promoteprogrammed death (apoptosis) of cultured prostate cancer cells (52, 53), the results ofepidemiological studies of cruciferous vegetable intake and prostate cancer risk are inconsistent.Four out of eight case-control studies published since 1990 found that some measure of cruciferousvegetable intake was significantly lower in men diagnosed with prostate cancer than men in acancer-free control group (54-57). Of the five prospective cohort studies that have examinedassociations between cruciferous vegetable intake and the risk of prostate cancer, none foundstatistically significant inverse associations overall (58-62). However, the prospective study thatincluded the longest follow-up period and the most cases of prostate cancer found a significantinverse association between cruciferous vegetable intake and the risk of prostate cancer when theanalysis was limited to men who had a prostate specific antigen (PSA) test (58). Since men whohave PSA screening are more likely to be diagnosed with prostate cancer, limiting the analysis inthis way is one way to reduce detection bias (63). Additionally, the most recent prospective studyfound that intake of cruciferous vegetables was inversely associated with metastatic prostatecancercancer that has spread beyond the prostate (i.e., late-stage prostate cancer) (62).Presently, epidemiological studies provide only modest support for the hypothesis that high intakesof cruciferous vegetables reduce prostate cancer risk (1).

Genetic Influences

There is increasing evidence that genetic differences in humans may influence the effects ofcruciferous vegetable intake on cancer risk (64). Isothiocyanates are glucosinolate hydrolysis




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products, which are thought to play a role in the cancer-preventive effects associated withcruciferous vegetable consumption. Glutathione S-transferases (GSTs) are a family ofenzymes thatmetabolize a variety of compounds, including isothiocyanates, in a way that promotes theirelimination from the body. Genetic variations (polymorphisms) that affect the activity of GSTenzymes have been identified in humans. Null variants of the GSTM1 gene and GSTT1 gene containlarge deletions, and individuals who inherit two copies of the GSTM1-null or GSTT1-null genecannot produce the corresponding GST enzyme (65). Lower GST activity in such individuals couldresult in slower elimination and longer exposure to isothiocyanates after cruciferous vegetable

consumption (66). In support of this idea, several epidemiological studies have found that inverseassociations between isothiocyanate intake from cruciferous vegetables and risk of lung cancer (16-19) or colon cancer (34-36) were more pronounced in GSTM1-null and/or GSTT1-null individuals.These findings suggest that the protective effects of high intakes of cruciferous vegetables may beenhanced in individuals who more slowly eliminate potentially protective compounds likeisothiocyanates. Alternatively, these same GSTs play a major role in detoxication of carcinogensand individuals with the null gene would be expected to be more susceptible to cancer; thus, thecruciferous vegetables may exhibit significant protection in this population if their protective effectis increasingly important at high carcinogen levels (67).

Nutrient Interactions

Iodine and Thyroid Function

Very high intakes of cruciferous vegetables, such as cabbage and turnips, have been found tocause hypothyroidism (insufficient thyroid hormone) in animals (68). There has been one casereport of an 88-year-old woman developing severe hypothyroidism and coma followingconsumption of an estimated 1.0 to 1.5 kg/day of raw bok choy for several months (69). Twomechanisms have been identified to explain this effect. The hydrolysis of some glucosinolates foundin cruciferous vegetables (e.g., progoitrin) may yield a compound known as goitrin, which has beenfound to interfere with thyroid hormone synthesis. The hydrolysis of another class ofglucosinolates, known as indole glucosinolates, results in the release of thiocyanate ions, which cancompete with iodine for uptake by the thyroid gland. Increased exposure to thiocyanate ions fromcruciferous vegetable consumption or, more commonly, from cigarette smoking, does not appear toincrease the risk of hypothyroidism unless accompanied by iodine deficiency. One study in humans

found that the consumption of 150 g/day (5 oz/day) of cooked Brussels sprouts for four weeks hadno adverse effects on thyroid function (70).

Intake Recommendations

Although many organizations, including the National Cancer Institute, recommend eating a varietyof fruits and vegetables daily (serving number depends on age, sex, and activity level; see (71)),separate recommendations for cruciferous vegetables have not been established. Much remains tobe learned regarding cruciferous vegetable consumption and cancer prevention, but the results ofsome epidemiological studies suggest that adults should aim for at least five weekly servings ofcruciferous vegetables (14, 58, 71).

Some Potentially Beneficial Compounds in Cruciferous (Brassica) Vegetables

Vitamins Minerals Phytochemicals

Folate Potassium Carotenoids

Vitamin C Selenium Chlorophyll

Fiber

Flavonoids

Indole-3-Carbinol




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Isothiocyanates

Lignans

Phytosterols

References

Written in July 2005 by:Jane Higdon, Ph.D.

Linus Pauling InstituteOregon State University

Updated in December 2008 by:Victoria J. Drake, Ph.D.Linus Pauling Institute

Oregon State University

Reviewed in December 2008 by:David E. Williams, Ph.D.

Principal Investigator, Linus Pauling InstituteProfessor, Department of Environmental and Molecular Toxicology

Oregon State University

Last updated 5/19/10 Copyright 2005-2012 Linus Pauling Institute

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The Linus Pauling Institute Micronutrient Information Center provides scientific information onhealth aspects of micronutrients and phytochemicals for the general public. The information ismade available with the understanding that the author and publisher are not providing medical,psychological, or nutritional counseling services on this site. The information should not be used in

place of a consultation with a competent health care or nutrition professional.

The information on micronutrients and phytochemicals contained on this Web site does not coverall possible uses, actions, precautions, side effects, and interactions. It is not intended as medicaladvice for individual problems. Liability for individual actions or omissions based upon the contentsof this site is expressly disclaimed.


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Crucifereos Vegetables