- Article Summary
- Main Article
The use of cruciferous vegetables—those in the cabbage family—began 7,000 years ago in China and spread throughout Europe during the Middle Ages. The oldest writings emphasize the medicinal utility of crucifers, but these vegetables have now gained culinary importance worldwide.
When raw crucifers are chewed, or when microwaved and steamed crucifers are digested by intestinal bacteria, they release substances called goitrogens that increase the need for iodine when consumed in small amounts and can damage the thyroid gland when consumed in large amounts.
These goitrogens also inhibit the transfer of iodine into mother’s milk.
Steaming crucifers until they are fully cooked reduces the goitrogens to one-third the original value on average. Since release of the goitrogens from steamed crucifers depends on intestinal bacteria, however, the amount released varies from person to person.
Boiling crucifers for thirty minutes reliably destroys 90 percent of the goitrogens.
Fermentation does not neutralize the goitrogens in crucifers. When foods like sauerkraut are consumed as condiments, however, the small amount of goitrogens within them is not harmful if one’s diet is adequate in iodine.
An increased dietary intake of iodine compensates for the consumption of moderate amounts of crucifers but cannot reverse the effects of large amounts of crucifers.
Paradoxically, the goitrogens found in crucifers may offer some protection against cancer. The jury is still out on whether or not this is true.
The use of sauerkraut as a condiment and several servings of steamed crucifers per week is probably beneficial. People who consume more than this amount, especially lactating mothers, should be sure to obtain extra iodine in their diet from seafood. People who make liberal use of crucifers on a daily basis should boil a portion of them to avoid excessive exposure to goitrogens.
The safety of concentrated sources of crucifer-related chemicals such as broccoli sprouts or supplements containing indole-3-carbinol (I3C) and 3-3′-diindolylmethane (DIM) is questionable. These supplements should be avoided until continuing research can further elucidate their risks and benefits.
Although cruciferous vegetables were not staple foods of our Paleolithic ancestors, they earned a reputation as medicinal plants among Greek and Roman civilizations and achieved widespread distribution throughout Europe during the Middle Ages. While cruciferous vegetables such as cabbage and broccoli are rich in many essential nutrients, they are distinguished for their abundance of chemical toxins called glucosinolates. Though they were once spurned as the predominant cause of goiter—a thyroid disease that in its most severe form produces a large swelling of the neck—many modern nutritionists now enthusiastically embrace glucosinolates as our most powerful insurance against a wide range of cancers.
Since crucifers paradoxically have the potential for both unique health benefits and unique toxicity, it is important to interpret the available science cautiously and to learn what lessons we can from the role that crucifers played and the way in which they were processed in traditional groups with proven immunity to degenerative diseases.
The word “crucifer” comes from the Latin crux (cross), and ferre, (to bear or carry).1 Although now called Brassicaceae, the eighteenth century Swedish taxonomist Carolus Linnaeus named the mustard family Crucif-erae because the flowers of its members bear four petals in the shape of a cross.2
Crucifers in History
The most widely used cruciferous vegetables belong to the genus Brassica and include broccoli, Brussels sprouts, cabbage, cauliflower, collard greens, kale, kohlrabi, mustard, rutabaga, turnip and bok choy. Other crucifers include arugula, horseradish, radish, wasabi and watercress.2 Lesser-known crops such as maca, a tuber used in the Andes, and Virginia pepperweed, used by some Mexican natives, are also crucifers.3 Even canola oil, derived from a close relative of the turnip, is a member of Cruciferae.4
Preserved brassica seeds unearthed in ancient Chinese villages date back to between 4000 and 5000 BC and in Pakistani villages to 2000 BC. Chinese and Sanskrit writings mention the use of brassicas in the first and second millennium BC. In the fifth and sixth centuries BC, the Greek writers Hippocrates and Pythagoras recorded the use of mustard as a condiment and as a remedy for scorpion stings. Evidence for the cultivation of cabbage, kale, broccoli and kohlrabi surfaces in writings of the early Roman Empire, while the first reliable references to cauliflower surface in Arab writings of the twelfth and thirteenth centuries. Crucifers spread across Europe during the Middle Ages as a result of the Crusades, travel across and around the Mediterranean Sea, and the prominence of the herb garden within monastic and village life.5
A number of leafy crucifers that no longer exist were used throughout Europe as salad vegetables and scurvy remedies from the sixteenth through the nineteenth centuries.3 Familiar crucifers such as cabbage, radish, turnip, mustard and horseradish also flourished throughout Europe by the sixteenth century.6 Cabbage itself reached cult status as a cure for all diseases.
According to Antonio Mizauld, a sixteenth century Parisian professor of medicine, the Germans and Flemish had a custom of consuming cabbage before and after meals, which protected them from being “overtaken by the wine which they never tire of drinking and with which they are always ready to moisten their throats.”6
Mizauld and some of his French and Italian contemporaries advised both young and old, even infants, to consume crucifers throughout life. Cabbage, according to these writings, could cure all things. The internal use of cabbage, especially mixed with wine, would cure a swollen spleen, pain of the heart, liver, lungs or any other internal organ, venomous snake bites and ulcers. Warm cabbage juice mixed with wine and dripped into the ears would cure hardness of hearing, while if it were mixed with fenugreek flour and applied as a plaster to the joints it would cure gout. Inhaled in its pure state, cabbage juice purged the brain; applied to the “natural parts of women,” it provoked menstruation. The topical application of cabbage leaves could subdue inflammation, remedy tumors, burst carbuncles, arrest hair loss, cleanse the skin of the face and even remove freckles.6
Other sixteenth century writers considered the turnip a remedy for parasites and an antidote to snake venom. Mustard soothed the kidneys and its seeds cured toothaches. Horseradish root mixed with white wine and bitter apple, heated, and then dripped into the ears eliminated buzzing sounds. If the same mixture were drunk with mead, according to these writings, it could cure jaundice.6
Crucifers continued to spread internationally in the following centuries. The first American settlers brought European crucifers to Jamestown.7 Kimchi, a Korean lacto-fermented dish made of miscellaneous vegetables dating back several thousand years, incorporated Chinese napa cabbage in the nineteenth century.8 Although some crucifers with very rigid environmental requirements such as Andean maca and true Japanese wasabi have remained local crops, most major food crops within the Cruciferae family have now spread throughout the world.
The Dark Side of Crucifers: Goitrogens
In 1929, researchers from Johns Hopkins University tempered the unbridled enthusiasm for crucifers that had characterized previous centuries of medical thought when they produced goiter in rabbits by feeding them cabbage. Goiter is a disease of the thyroid gland best known for the swollen protrusions of the neck that often accompany it. Although an excess of iodine can also produce the disease, goiter usually results from a deficiency of iodine or excessive exposure to chemicals found in food or the environment called goitrogens. Iodine deficiency goiter is associated with a disease called cretinism that results in impaired growth and mental development, while goitrogen-induced goiter is associated with autoimmune thyroiditis, hypo- or hyperthyroidism, and thyroid cancer.9
At low concentrations, the goitrogens in cabbage and other crucifers inhibit the uptake of iodine by the thyroid gland; this effect can be overcome by an increased dietary intake of iodine. At high concentrations, however, these chemicals inhibit the incorporation of iodine into thyroid hormone. In this case, even the iodine that makes it into the thyroid gland cannot be used; dietary iodine therefore cannot overcome the effect of very large amounts of crucifers.9
Cruciferous goitrogens also inhibit the transfer of iodine into milk by the mammary gland. The goitrogens themselves cross the placenta into the fetal bloodstream during pregnancy and pass into the maternal milk during lactation.10 Milk from cows grazing on especially goitrogen-rich crucifers resulted in an outbreak of goiter in Finland in the 1960s,9 and researchers believe that high maternal consumption during pregnancy and lactation of improperly detoxified cassava—a starchy vegetable with goitrogens similar to those that occur in crucifers—plays a role in the endemic cretinism that plagues the children of many third world populations.10
Research on adverse effects of crucifers has largely focused on the effects of rapeseed meal in cattle, poultry and pork animals. Scientists began developing low-goitrogen varieties of the meal in the 1980s after it was found to cause hypothyroidism and reduced food intake and growth.4 However, research has not addressed the question of whether crucifers might cause hypothyroidism in humans in the absence of goiter.11
Humans generally do not consume rapeseed meal, which is very high in a particularly noxious goitrogen called goitrin. Goitrin is especially toxic because the body does not degrade it as well as other goitrogens.9 Perhaps the apparent uniqueness of rapeseed’s toxicity as well as the belief that sufficient intake of iodine can overcome any adverse effects of most crucifers10 has resulted in the relative lack of concern. Researchers from the University of Calcutta, however, showed in 2006 that a diet composed of 30 percent radish—which does not contain goitrin12 —produces hypothyroidism, derangement of the cells of the thyroid gland and increased thyroid weight typical of goiter, even when cooked and accompanied by very large intakes of iodine.13
Because feeding goitrogens to animals can produce thyroid cancer, a number of research groups have investigated the potential association between cruciferous vegetables and this disease. To date, all of them have been case control studies, which are subject to several types of bias because they select the participants and collect the dietary information after the diseases have already been diagnosed. A recent analysis pooled together the results of eleven of these studies and concluded that “high” intakes of crucifers had no association with thyroid cancer.14
But a closer look at this analysis raises a red flag. In some studies included within it, a “high” intake of crucifers was defined as more than several servings per year; in others, it was defined as more than three, six or eight servings per month; in yet others it was defined as more than one or four servings per week; only in one study was a “high” intake of crucifers considered to be more than one serving per day. This final study was conducted in Japan and found a 56 percent increased risk of thyroid cancer associated with an intake of more than 8.5 servings of cruciferous vegetables per week.14 This study ran contrary to the majority of those included, which found decreased risks. Although a single case control study certainly is not grounds for a confident conclusion, it raises the question of whether low intakes of crucifers may offer some protection against thyroid cancer while consistent daily intake of crucifers may be harmful.
The Dark Side of Crucifers: Nitriles
In addition to goitrogens, crucifers also contain substances called nitriles that can release cyanide into tissues and result in general toxicity at high doses.15 A 2004 study conducted in Japan suggested that massive doses of nitriles, doses that are impossible to obtain from food, would be required in order to result in toxicity.16 This study used behavioral endpoints such as restlessness to judge toxicity.
A Dutch study conducted in 1991 had already shown that toxicity can result with levels of nitriles easily achieved by feeding Brussels sprouts. Ten percent of the diet as Brussels sprouts by dry weight produced decreased food intake, growth depression, increased kidney weight and impaired kidney function in rats. This was substantially less than the 15 percent required to decrease levels of thyroid hormone. A 5 percent Brussels sprout diet increased liver weight, and a diet containing just 2.5 percent Brussels sprouts increased blood clotting.17 Although the study could not rule out effects of other chemicals in the sprouts, liver and kidney toxicity is characteristic of nitrile poisoning.15
According to laboratory simulations of digestion, Brussels sprouts generate five to ten times the amount of nitriles as broccoli, ten to thirty times the amount of nitriles as cabbage, and nearly seventy times the amount of nitriles found in sauerkraut. Of those crucifers that have been tested, only the stems and leaves of young broccoli plants approach the nitrile content of Brussels sprouts, generating between one-third and one-half as much upon digestion.16,18
In a recent double-blind, placebo-controlled trial of the short-term safety of broccoli sprouts, four out of nine subjects consuming either twelve-gram or fifty-gram servings of the sprouts for seven days developed abnormal levels of liver enzymes, indicating possible liver toxicity. Two of the subjects developed the abnormal readings after the researchers released them from the study for two days, and only one of the subjects experienced the repeated abnormal readings required to diagnose clinical liver toxicity. Although the researchers could therefore not attribute any clear and consistent toxicity to the sprouts, the fact that none of the three placebo subjects developed abnormal levels of liver enzymes suggested a causal relationship.19 Broccoli sprouts are ten to one hundred times as rich as broccoli in chemicals that can potentially release nitriles upon digestion.20 Prudent observers may wish to wait for the completion of long-term safety studies before offering themselves as guinea pigs for this newfangled food.
Cooking, Fermentation and Other Processing
Throughout history, various populations have prepared cruciferous vegetables in different ways, some of which neutralize the goitrogens to varying extents and some of which do not. Many people believe that cooking and fermenting crucifers eliminates the goitrogens but the situation is much more complex than this.
Fermentation of sauerkraut actually activates the goitrogens from their precursors. It also has the beneficial effect of reducing the nitrile content to half of what would be generated by cabbage upon digestion.18,21 Since nitriles appear to be more toxic than goitrogens and their effects cannot be mitigated by dietary iodine, the overall effect of fermentation is positive. More importantly, if sauerkraut is used as a condiment, the amount of goitrogens consumed is very low and very unlikely to exert any harm. However, it is important to realize that unreasonably high intakes of sauerkraut could have adverse effects.
Most forms of cooking reduce but do not eliminate the goitrogenic effect. Microwaving cabbage reduces the goitrogen bioavailability to one-half; steaming broccoli reduces it to one-third; and boiling watercress reduces it to one-tenth. Boiling not only leaches goitrogens into the cooking water, but also brings the vegetable to a higher temperature, causing a greater thermal destruction of the goitrogens within it. Boiling cabbage for just five minutes results in a 35 percent loss of goitrogen activity; thereafter, each additional five minutes results in another five to ten percent loss. By thirty minutes of boiling, 87 percent of the goitrogens are eliminated. Cooking also greatly reduces the formation of nitriles.22
Although cassava is not a crucifer, it contains goitrogens that are chemically similar to those found in crucifers. Since many African groups rely on cassava as a major staple, it is instructive for us to consider how they prepare it. In the groups of Central Africa where the prevalence of goiter is low, the natives soak the cassava roots in river water for two to six days before mashing them into a purée, simmering them into a paste, and wrapping them in palm or banana leaves. The cassava leaves are boiled before cooking. Other groups do not soak the cassava roots; instead they peel them, dry them in the sun, pound them with soaked corn and eat them as gruel. In contrast to the groups who soak the cassava, those who do not have a high prevalence of goiter.10
Crucifers and Cancer
In recent years, enthusiasm of the medical and nutritional professions for crucifers has resurfaced with the intensive investigation of the hypothesis that crucifer consumption may protect against cancer. Ironically, the chemicals to which researchers now attribute this anti-carcinogenic effect are the very same chemical toxins that we have known for so long as goitrogens.
The anti-carcinogen hypothesis is driven by three observations: first, the chemical toxins in crucifers stimulate enzymes responsible for their own detoxification and may thereby increase the rate of detoxification of carcinogens that are cleared by the same enzymes; second, a number of these chemicals are extremely toxic to cancer cells and can therefore act as chemotherapeutic agents (see sidebar on page 42); third, epidemiological evidence suggests that people who eat more cruciferous vegetables have a lower risk of various cancers.
In 1996, researchers from the University of Limburg in the Netherlands published a comprehensive review of the 94 studies that had been conducted on the relationship of brassica vegetables to cancer risk.24 Each study included was one of two types: retrospective case control studies or prospective cohort studies.
Case control studies select people who have been diagnosed with a disease (cases) and people who have not (controls), and then ask them to recall their past dietary habits. Because they are retrospective, they are subject to two types of bias to which prospective cohort studies are not: selection bias and recall bias. Selection bias may result if people who are more health conscious—who eat more cruciferous vegetables, for example—are more interested in volunteering to be control subjects than those who are less health conscious. Recall bias may result if people who were diagnosed with a disease are more conscious of the habits they perceive to be unhealthy and to have contributed to their disease—lack of vegetable consumption, for example—while those without the disease may emphasize their healthier habits. Case control studies can therefore serve to reinforce preconceived cultural definitions of what constitutes a healthy diet and lifestyle.
Prospective cohort studies collect dietary information from a group of healthy people before any of them develop the disease being studied. Then, the researchers track these people for a number of years and record who among them develops the disease. Cohort studies are thus much more reliable than case control studies because the information is collected at a point during which neither the researchers nor the subjects know who will develop the disease and who will not. Unfortunately, cohort studies are also more costly and time-consuming. Case control studies greatly outnumber cohort studies: in the 1996 comprehensive review, 87 out of 94 studies included were case control studies while only seven were cohort studies.
Among the case control studies, 67 percent found an inverse association between the consumption of at least one brassica vegetable and the risk of cancer, while only 16 percent found a positive association. The findings of the prospective cohort studies were much less impressive. The seven studies generated thirteen correlations between either brassicas as a group or individual brassica vegetables and cancer risk. Six of these associations (46 percent) showed a lower risk of cancer for higher consumption of brassicas, four (31 percent) showed increased risk, and three (23 percent) were neutral.
In the decade since the publication of that review, researchers have published numerous prospective cohort studies with ambivalent results. Two studies showed inverse associations with lung cancer, one failed to show an association, and one showed an inverse association in women but not in men. Four studies failed to demonstrate an inverse association with colorectal cancer, while a fifth found that people who consumed the equivalent of 2.5 cups of crucifers per week had a decreased risk of colon cancer but an increased risk of rectal cancer compared to those who consumed the equivalent of one-half cup per week.2 A pooled analysis of eight studies on the relationship between fruit and vegetable consumption and breast cancer showed no relationship with crucifers.25 None of four studies showed an inverse association with prostate cancer, but one of them found a 28 percent reduced risk for the consumption of five servings of crucifers per week compared to one serving per week when they limited the analysis to men who were diagnosed with the prostate specific antigen (PSA) test, which is considered a more sensitive diagnostic measurement. Finally, one study associated the consumption of one or more servings of cabbage per week compared to never eating cabbage with a 38 percent reduced risk of pancreatic cancer.2
The current cutting-edge hypothesis explaining the association between cruciferous vegetables and cancer is that crucifers primarily confer benefit upon people who for genetic reasons exhibit a very sluggish rate of detoxification. There are two competing explanations for this phenomenon: crucifer toxins “wake up” the sluggish detoxification and raise it to a normal level in these people, in turn eliminating their increased risk for cancer; alternatively, cancer cells within the tissues of those who detoxify the cruciferous chemicals more slowly will be exposed to their anti-carcinogenic effects for a longer period of time. This hypothesis has gained substantial support but has also encountered surprising contradictions (see sidebar on page 43).
It will be interesting to see what the continued investigation into these hypotheses can tell us about the relationship between crucifers and cancer. In the mean time, however, we would be wise to interpret the uncertainty within the context of our understanding of the primitive diets that we know have produced superb health in those consuming them.
Crucifers in Primitive Diets
Crucifers and other green vegetables did not figure prominently as staples in the diets of the groups that Weston Price studied. Price estimated that the Swiss of the Loetschental Valley ate five percent of their calories as vegetables and had access to greens only during the summer. The Gaelics of the Outer Hebrides did not eat substantial amounts of vegetables at all. Kelp, berries, sorrel grass and flower blossoms comprised the plant foods of the Eskimo. Price mentions little of the plant foods of the North American Indians; modern researchers have recorded the use of a variety of crucifers by natives indigenous to Canada but they played a minor, seasonal role in the diet. Taro was the most common plant food in the islands of the Pacific. The most common plant food Price recorded in use among the African groups he examined was the banana; the sweet potato followed closely behind; and cereal grains and legumes also played an important role.
Price did not write much about the plant foods of the Australian Aborigines, but modern researchers believe the traditional Aboriginal diet supplemented its animal foods primarily with fruits, roots, tubers, nuts and seeds. Vegetables played a minor role. The Aborigines considered most of the leaves eaten by early European settlers to be inedible.39 Price primarily listed fruits among the plant foods of the Torres Strait Islanders and described the intensive use of kelp and fern roots among the Maori. He attributed grains, beans, potatoes and squash to the ancient Peruvians; to the modern Peruvians he primarily attributed corn, beans and yucca, though he noted the use of an assortment of fruits and vegetables that he did not name in detail. Peruvians and their Bolivian neighbors did in fact use a cruciferous tuber called maca, but the great difficulty with which maca is grown rendered it a minor crop.3
Even as minor components of the diet, however, some crucifers can make important contributions. Brassicas such as broccoli, kale and bok choy contain several times as much calcium as milk per calorie and about half as much per unit of volume; the bioavailability of calcium from these vegetables is slightly better than that from pasteurized milk and over ten times better than that from spinach.40,41 They are rich in vitamin C, vitamin K1, beta-carotene and other nutrients and pigments. When used as a condiment, sauerkraut can provide beneficial enzymes, bacteria and various nutrients produced during fermentation.
It seems unlikely that the use of small amounts of sauerkraut as a condiment or several servings of steamed crucifers per week would exert adverse effects on the thyroid, and it is possible—though far from proven—that small amounts of the goitrogenic chemicals within them do in fact have some health benefits. At the same time, it may be wise for the nursing mother to practice strict moderation in the consumption of crucifers or to be sure to obtain extra iodine in the diet from the liberal use of fish and seaweed if she consumes them regularly, to insure that her infant obtains optimal amounts of iodine from her milk.
According to the United States Department of Agriculture, green vegetables retain most of their nutrients when we boil them and drain the water. They do lose, however, 45 percent of the vitamin C, 20 percent of the thiamin and 40 percent of the folate.42 If one makes liberal use of crucifers on a daily basis it may be wise to boil them rather than steaming them, especially if one has any signs of thyroid problems. This is especially true of Brussels sprouts, which produce much higher levels of cyanide-generating nitriles than the other crucifers.
This is a minority view. Crucifers are currently widely extolled, not despite their toxins but because of them. Dr. Joel Fuhrman argues in Eat to Live that much of the scientific evidence is conflicting because we simply do not eat enough crucifers and other green leafy vegetables to experience their full range of health-promoting effects. He recommends eating a minimum of two pounds per day of leafy vegetables and places crucifers at the top of his nutrient density ranking because he counts their glucosinolates as nutrients rather than toxins. Although Fuhrman may represent the opposite extreme, many more moderate authors recommend several servings per day of crucifers to obtain the putative benefits of glucosinolates.
It is not difficult, however, to find the contrary view expressed in other parts of the world where crucifer consumption is much higher than in ours. In Indian journals, for example, crucifers are blamed for the endemic goiter that iodine fortification has failed to eliminate.13 In Japan, crucifer consumption may be associated with thyroid cancer.14
Many of the groups Price studied ate little in the way of green vegetables and even less in the way of crucifers, yet exhibited a remarkable immunity to cancer. While crucifers may make important contributions as minor constituents of some diets, it would be a mistake to jump on the current bandwagon exaggerating their role in cancer prevention and promoting newfangled and experimental foods like broccoli sprouts rich in chemicals that our ancestors would have leached into running water for days to eliminate. We should learn our lessons about how to prevent cancer not from the subtle distinctions between various states of disease we observe in our own society but from groups like the Torres Strait Islanders, the Eskimos and the North American Indians whose physicians went decades at a time unable to find a single case of cancer among them. The traditions that these groups kept bore fruit, by which we know that they continue to bear wisdom.
Summary of Toxins from Crucifers
Present in cruciferous vegetables
- Stimulate free radical damage when fed to animals.
- Resistant to steaming and microwaving.
- Eliminated by boiling.
Formed from Glucosinolates
- Chewing if the vegetable is raw.
- Bacterial fermentation if the vegetable is raw, steamed, or microwaved.
Formation affected by:
- Light heating increases the formation.
- Formation highest under neutral or mildly acidic conditions.
- Stimulate detoxification enzymes.
- Interfere with DNA segregation during mitosis, resulting in cell death.
- Thiocyanate ions (large amounts).
- Thioureas (small amounts).
Formed from Isothiocyanates
- Spontaneous formation within the body.
- Extended fermentation (greater than two weeks).
- Inhibit iodine uptake by thyroid and mammary glands.
- Effects overcome by dietary iodine.
Formed from Isothiocyanates
- Spontaneous formation within the body.
- Inhibit synthesis of thyroid hormone.
- Effects are not overcome by dietary iodine.
Formed from Glucosinolates
- Chewing if the vegetable is raw.
- Bacterial fermentation if the vegetable is raw, steamed or cooked.
Formation affected by:
- Light heating increases the formation.
- Formation highest under neutral or mildly acidic conditions.
- Inhibit ATP production.
- Conflicting effects on estrogen metabolism.
Formed from Glucosinolates
- Chewing if the vegetable is raw.
- Bacterial fermentation if the vegetable is raw, steamed, or microwaved.
Formation affected by:
- Light heating decreases the formation.
- Fermentation of sauerkraut decreases the formation.
- Formation highest under strongly acidic conditions.
- Stimulate detoxification enzymes.
- Cyanide-related toxicity resulting in decreased food intake, impaired kidney function, impaired energy production, increased blood clotting and increased liver weight. Can result from cooked Brussels sprouts.
- Very large doses cause restlessness. Unlikely to result from food.
Glucosinolates and Processing: A Closer Look
The goitrogens found in cruciferous vegetables are called glucosinolates. These chemicals contain glucose, sulfur and cyanide combined into a single molecule. Glucosinolates are not actually goitrogenic themselves but are precursors to the active goitrogens and to other toxins.15
Glucosinolates are accompanied by the enzyme myrosinase within the plant; the myrosinase, however, is segregated from the glucosinolate in a separate compartment. When insects attack the plant or when humans chew it in its raw state, the enzyme myrosinase breaks free from its compartment and converts the glucosinolates into isothiocyanates, indoles and nitriles. (See Sidebar, page 36.) Since the breakdown products of glucosinolates tend to be toxic to the plant as well as to insects, the plant holds them as inactive precursors until they are needed for its defense.15
Isothiocyanates undergo normal metabolism within the body to produce thiocyanate ions and thioureas. Thiocyanate ions are produced to a greater extent than thioureas, and these inhibit iodine uptake into the thyroid gland; dietary iodine can overcome this effect. Thioureas, by contrast, block the enzyme that incorporates iodine into thyroid hormone; dietary iodine cannot overcome this effect. Since one must consume large amounts of isothiocyanates in order to generate a substantial amount of thioureas, dietary iodine can overcome the effects of low isothiocyanate intakes but not high isothiocyanate intakes.9
Both indoles23 and nitriles15 inhibit the cell’s ability to produce its universal energy currency, ATP. Indoles accomplish this by generating 3,3′-Diindolylmethane (DIM) within the acidic environment of the stomach, while nitriles accomplish this by releasing cyanide into cells. Cyanide inhibits the enzyme that uses oxygen to harvest energy from food molecules, while DIM inhibits the enzyme that uses that energy to synthesize ATP.
In a neutral or mildly acidic environment, the glucosinolates will break down into either isothiocyanates or indoles. Most glucosinolates in the food we eat yield the former while a minority yields the latter. Under more acidic conditions, glucosinolates break down into nitriles.22
In addition to myrosinase, the plant also contains a protein called epithiospecifier protein (ESP) that encourages the formation of nitriles rather than isothiocyanates. Mild heat that brings the internal temperature of the vegetable to 50°C destroys ESP. Thus, light cooking substantially reduces the yield of nitriles and increases the yield of isothiocyanates. Bringing the internal temperature of the vegetable to between 90°C and 100°C completely destroys the enzyme myrosinase. Therefore, glucosinolates cannot be broken down through chewing once the vegetable is fully cooked. However, intestinal bacteria such as Lactobacilli, Bifididobacteria, and Bacterioides can break down glucosinolates into isothiocyanates, indoles and nitriles, as well as other chemicals called amines once they pass into the small intestine and colon.22
A cruciferous vegetable that is fully cooked by steaming yields, on average, one-third the amount of isothiocyanates as the raw vegetable would yield. Since intestinal bacteria are widely variable, however, there is a four-fold variation between individuals. No studies have yet quantified what proportion of the glucosinolates from steamed vegetables yield other byproducts such as indoles and nitriles in humans. In contrast to steaming, boiling not only leaches glucosinolates into the water, but can also raise the internal temperature of the vegetable up to 110 degrees C, at which point the thermal degradation of glucosinolates begins. A half hour of boiling produces a nearly 90 percent loss of glucosinolates.22 Extended boiling is therefore the only way to avoid exposure to isothiocyanates, indoles and nitriles.
Fermentation of sauerkraut for three to five days fully converts the glucosinolates into isothiocyanates and nitriles; very little indole is found in sauerkraut.18 Fermentation for two weeks or longer fully converts the isothiocyanates into thiocyanate ions.21 Regardless of the length of time, fermentation reduces the amount of nitriles formed to half of what would be expected. Since sauerkraut is consumed in small amounts as a condiment, it is unlikely to exert adverse effects. Since sauerkraut provides important nutrients, enzymes and bacteria, it can serve as an important contribution to a healthy diet.
The Effects of Agriculture on the Glucosinolate Content of Crucifers
The amount and type of glucosinolates—the precursors to goitrogens and the plant’s natural pesticides—varies with the plant’s age, its environment, and the agricultural practices with which it is grown.
As a plant matures, its level of glucosinolates declines dramatically. The content of thiocyanate, a breakdown product of glucosinolates, is five times higher in the small young leaves of kale than in the fully formed mature leaves.15 The glucosinolate content of broccoli sprouts is ten to one hundred times that of mature broccoli.20
One study showed that organic crops have 15 to 40 percent higher average levels of glucosinolates than conventional crops. Infections of seeds or plants by fungi, parasitic insects or other pests can double the content of glucosinolates. Drought or inadequate water increases the level, and boron deficiency can triple it. In general, glucosinolate concentrations appear to increase in response to stress. Additionally, small molecules such as sugars and amino acids may accumulate and form glucosinolates when the plant does not have sufficient nutrients to incorporate them into larger structures such as proteins and cellulose.15
The glucosinolates in cruciferous vegetables break down into several compounds that have potent anti-carcinogenic activities. The most widely studied of these are the isothiocyanate sulforaphane, which is a breakdown product of the glucosinolate glucoraphanin, and indole-3-carbinol, which is a breakdown product of indole glucosinolates.
Sulforaphane is the most powerful activator known of the detoxification enzyme glutathione S-transferase, which detoxifies carcinogens and other chemicals by attaching glutathione to the toxin, making it less dangerous, more water-soluble and easier to excrete. Sulforaphane also mildly increases the production of glutathione as well, and is itself detoxified by glutathione.26 Milk thistle, which has been used to treat liver diseases for hundreds of years, green tea27 and coffee28 have similar effects on the glutathione S-transferase enzyme.
Sulforaphane has captured the interest of researchers not only because it is such a powerful activator of glutathione S-transferase, but also because it does not increase the activity of other liver detoxification enzymes called “phase 1” enzymes that, when elevated to inappropriate levels, increase the concentration of dangerous free radicals within the cell. Somehow amidst all of the excitement many researchers seem to have forgotten the fact that we do not eat sulforaphane in foods but rather its precursor, glucoraphanin, which can be converted into a number of other products besides sulforaphane. Last year Italian researchers published the first study examining the effects of feeding purified glucoraphanin to rats. The doses they used were extreme and much higher than one would encounter in natural foods, so do not provide a basis for a solid conclusion. Nevertheless, the glucoraphanin produced only a slight increase in gluathione S-transferase and an enormous increase in phase 1 enzymes that resulted in 10-fold and 22-fold increases in the levels of free radicals, depending on the dose. The authors concluded that it might be dangerous to seek out this particular compound rather than simply eating a diet rich in a diversity of fruits and vegetables.29
Sulforaphane itself has been known for years to produce the death of cancer cells and to quench their ability to reproduce. Newer research is examining the role of sulforaphane in preventing a process called angiogenesis whereby cancer cells establish a rich blood supply with the growth of new blood vessels. A startling paper published this February in the journal Vascular Pharmacology elucidated the mechanism by which sulforaphane exerts these effects. In it, researchers from the University of Illinois showed that sulforaphane disrupts the formation of microtubules, which are used in mitosis (cellular reproduction) to pull chromosomes to either side of the cell as it begins to split in two. The genetic material then becomes disorganized and the cell commits suicide. The researchers demonstrated their results not in cancer cells but in normal cells that line the aorta, showing how sulforaphane could inhibit the ability of these cells to reproduce and form new blood vessels. The authors noted that the action did not seem specific for particular cell types and “may pose a toxicity issue for other tissues undergoing normal growth and development.” They suggested studying the phenomenon further within other non-cancerous tissues and within live animals to define any potential risk of toxicity.30
Indole glucosinolates release indole-3-carbinol upon chewing or fermentation; under acidic environments such as the stomach, two molecules of this indole will combine with one another to produce 3,3′-Diindolylmethane (DIM). In every type of cell tested, including non-cancerous cells, DIM acts as a potent inhibitor of the enzyme that synthesizes the universal energy currency, ATP. This results in oxidative stress, the depletion of glutathione, and the cessation of cellular reproduction.23
Indole-3-carbinol and DIM both activate enzymes involved in detoxification and DNA repair.31 Indole-3-carbinol possesses a very weak ability to damage DNA itself.32 When administered before or at the same time as a carcinogen, it inhibits the growth of cancers of the breast, stomach, colon, lung and liver. When administered after a carcinogen, however, it promotes the growth of cancers of the liver, thyroid, colon and uterus.2
Sulforaphane and indole-3-carbinol are both anti-viral and anti-bacterial. Sulforaphane has effectively treated some cases of Helicobacter pylori infections, and indole-3-carbinol has effectively treated some cases of pre-cancerous cervical lesions2 and recurrent respiratory papillomatosis,31 both associated with the human papilloma virus. Nevertheless, a number of researchers have cautioned against the widespread use of indole-3-carbinol and DIM supplements until it can be clarified whether these compounds act as anti-carcinogens or pro-carcinogens in humans.2
Crucifers, Chromosomes and Cancer
Isothiocyanates are derived from the glucosinolates found in cruciferous vegetables. On the one hand, these chemicals increase the production of the important detoxification enzyme glutathione S-transferase (GST) while on the other hand they are themselves detoxified by GST. A number of groups of researchers have therefore begun investigating whether or not genetic alterations in this enzyme may affect the relationship between cruciferous vegetables and the risk of cancer. The consensus has favored the expectation that people with low GST activity will benefit most from crucifer consumption, but for two different reasons: some researchers have suggested that crucifers will serve to “wake up” the sluggish GST enzyme in these people and eliminate their increased risk for cancer, while others have suggested that these people will detoxify isothiocyanates more slowly and will therefore be exposed to their anti-carcinogenic effects for a longer period of time.
Research in this area is new and is currently far from perfect. The investigation of these hypotheses is confounded by several complications. For example, there are actually a number of different GST subtypes that are produced by each individual such as GSTM1, GSTT1, GSTP1 and GSTA1. Each of these subtypes can have a number of different mutations leading to decreased activity or even complete absence of the enzyme. Thus far, studies have only evaluated one or two of these subtypes and no single study has evaluated all of them together.
Several studies have shown that crucifer consumption is associated with a much lower risk of lung cancer in those who possess no active GSTM1 or GSTT1. Two studies showed that crucifers were only associated with a lower risk of colorectal cancer in those lacking these enzymes.33 Another study, however, showed that the M1 and T1 forms had no effect and those who had low GSTP1 activities had an increased risk of colorectal cancer with increasing crucifer intake, although the study did not have the statistical power to completely rule out an effect of chance on the association.34
Researchers associated a 51 percent decrease in the risk of prostate cancer with crucifer consumption among those who possessed an active GSTM1 enzyme but associated a 51 percent increase in risk among those who possessed an inactive GSTT1 enzyme.35 One study associated a high intake of crucifers with a 40-49 percent decrease in the risk of bladder cancer among smokers regardless of genetics; the same study associated an increased risk with increasing crucifer intake among never smokers who had inactive GSTM1 or GSTT1 and a reduced risk among never smokers who had active GSTM1 or GSTT1, although it was not statistically powerful enough to conclusively rule out an effect of chance.36 Finally, consumption of four servings of crucifers per week reduced the risk of breast cancer in the 17 percent of subjects in the Long Island Breast Cancer Study Project who had a low-activity form of GSTA1 and produced a slight increase in risk among the other subjects; a high crucifer intake did not confer any special advantage on this 17 percent but did return their otherwise elevated risk of breast cancer to normal.37
Researchers from the Universities of North and South Carolina only confused matters more when they recently announced the unexpected finding that people with an inactive GSTM1 enzyme actually excrete isothiocyanates at a faster rate, not a slower one.38 The only conclusion that can be drawn from these studies at the present time is that the new millennium has shown the relationship between cruciferous vegetables and cancer to be far more complicated than anyone in the 1990s had ever expected.
- Wikipedia. Crucifer. http://en.wikipedia.org/wiki/Crucifer. Accessed April 16, 2007.
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- Collonial Williamsburg. Brassicas. http://www.history.org/history/CWLand/resrch3.cfm Accessed April 16, 2007.
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- Vanderpas J. Nutritional epidemiology and thyroid hormone metabolism. Annu Rev Nutr. 2006; 26: 293-322.
- An April 16, 2007 search of www.pubmed.com for the keywords “crucifer TSH,” “cruciferous TSH,” “brassica TSH,” “crucifer hypothyroidism,” “cruciferous hypothyroidism,” and “brassica hypothyroidism” did not yield any human studies addressing associations between crucifer intake and TSH levels or clinical hypothyroidism in humans.
- Fahey JW, Zalcmann AT, Talalay P. The chemical diversity and distribution of glucosinolates and isothiocyanates among plants. Phytochemistry. 2001; 56: 5-51.
- Chandra AK, Mukhopadhyay S, Ghosh D, Tripathy S. Effect of radish (Raphanus sativus Linn.) on thyroid status under conditions of varying iodine intake in rats. Indian J Exp Biol. 2006; 44: 653-661.
- Bosetti C, Negri E, Kolonel L, Ron E, Franceschi S, Preston-Martin S, et al. A pooled analysis of case-control studies of thyroid cancer. VII. Cruciferous and other vegetables (International). Cancer Causes Control. 2002; 13: 765-775.
- Rosa EAS, Heaney RK, Fenwick GR, Portas CAM. Glucosinolates in Crop Plants. Hort Rev. 1997; 19: 99-215.
- Tanii H, Takayasu T, Higashi T, Leng S, Saijoh K. Allylnitrile: generation from cruciferous vegetables and behavioral effects on mice of repeated exposure. Food Chem Toxicol. 2004; 42: 453-458.
- De Groot AP, Willems MI, de Vos RH. Effects of high levels of brussels sprouts in the diet of rats. Food Chem Toxicol. 1991; 29(12): 829-37.
- Tolonen M, Taipale M, Viander B, Pihlava J-M, Korhonen H, Ryhänen E-L. Plan-Derived Biomolecules in Fermented Cabbage. J Agric Food Chem. 2002; 50: 6798-6803.
- Shapiro TA, Fahey JW, Dinkova-Kostova AT, Holtzelaw D, Stephenson KK, Wade KL, Ye L, Talalay P. Safety, Tolerance, and Metabolism of Broccoli Sprout Glucosinolates and Isothiocyanates: A Clinical Phase I Study. Nutr Cancer. 2006; 55(1): 53-62.
- Fahey JW, Zhang Y, Talalay P. Broccoli sprouts: an exceptionally rich source of inducers of enzymes that protect against chemical carcinogens. Proc Natl Acad Sci USA. 1997; 94(19): 10367-72.
- Daxenbichler ME, VanEtten CH, Williams PH. Glucosinolate Products in Commercial Sauerkraut. J Agric Food Chem. 1980; 28(4): 809-811.
- Rungapamestry V, Duncan AJ, Fuller Z, Ratcliffe B. Effect of cooking brassica vegetables on the subsequent hydrolysis and metabolic fate of glucosinolates. Proc Nutr Soc. 2007; 66: 69-81.
- Gong Y, Sohn H, Xue L, Firestone GL, Bjeldanes LF. 3-3′-Diinolylmethane Is a Novel Mitochondrial H+-ATP Synthase Inhibitor that Can Induce p21Cip1/Waf1 Expression by Induction of Oxidative Stress in Human Breast Cancer Cells. Cancer Res. 2006; 66(9): 4880-7.
- Verhoeven DTH, Goldbohm RA, van Poppel G, Verhagen H, van den Brandt PA. Epidemiological Studies on Brassica Vegetables and Cancer Risk. Cancer Epidemiol Biomarkers Prev. 1996; 5(9): 733-48.
- Smith-Warner SA, Spiegelman D, Shiaw-Shyuan Y, Adami H-O, Beeson WL, van den Brandt PA, et al. Intake of Fruits and Vegetables and Risk of Cancer. JAMA 285: 769-776.
- Brooks JD, Paton VG, Vidanes G. Potent Induction of Phase 2 Enzymes in Human Prostate Cells by Sulforaphane. Cancers Epidemiol Biomarkers Prev. 2001; 10: 949-954.
- Moon YJ, Wang X, Morris ME. Dietary flavonoids: Effects on xenobiotic and carcinogen metabolism. Toxicol In Vitro. 2006; 20: 187-210.
- Huber WW, Parzefall W. Modification of N-acetyltransferases and glutathione S-transferases by coffee components: possible relevance for cancer risk. Methods Enzymol. 2005; 401: 307-41.
- Perocco P, Bronzetti G, Canistro D, Valgimigli L, Sapone A, Affatato A, Pedulli GF, et al. Glucoraphanin, the bioprecursor of the widely extolled chemopreventive agent sulforaphane found in broccoli, induces Phase-I xenobiotic metabolizing enzymes and increases free radical generation in rat liver. Mutat Res. 2006; 595: 125-136.
- Jackson SJT, Singletary KW, Venema RC. Sulforaphane suppresses angiogenesis and disrupts endothelial mitotic progression and microtubule polymerization. Vascul Pharmacol. 2007; 46: 77-84.
- Rogan EG. The Natural Chemopreventive Compound Indole-3-Carbinol: State of the Science. In Vivo. 2006; 20: 221-228.
- Doppalapudi RS, Riccio ES, Rausch LL, Shimon JA, Lee PS, Mortelmans KE. Mutat Res. 2007; doi:10.1016/j.mrgentox.2007.02.004.
- Seow A, Vainio H, Yu MC. Effect of glutathione S-transferase polymorphisms on the cancer preventive potential of isothiocyanates: An epidemiological perspective. Mutat Res. 2005; 592: 58-67.
- Tijhuis MJ, Wark PA, Aarts JMMJG, Visker MHPW, Nagengast FM, Kok FJ, Kampman. GSTP1 and GSTA1 Polymorphisms Interact with Cruciferous Vegetable Intake in Colorectal Adenoma Risk. Cancer Epidemiol Biomarkers Prev. 2005; 14(12): 2943-51.
- Joseph MA, Moysich KB, Freudenheim JL, Shields PG, Bowman ED, Zhang Y, Marshall JR, Ambrosone CB. Cruciferous vegetables, genetic polymorphisms in glutathione S-transferases M1 and T1, and prostate cancer risk. Nutr Cancer. 2004; 50(2): 206-13.
- Zhao H, Lin J, Grossman HB, Hernandez LM, Dinney CP, Wu X. Dietary isothiocyanates, GSTM1, GSTT1, NAT2 polymorphisms and bladder cancer risk. Int J Cancer. 2007; 120: 2208-2213.
- Ahn J, Gammon MD, Santella RM, Gaudet MM, Britton JA, Teitelbaum SL, et al. Effects of glutathione S-transferase A1 (GSTA1) genotype and potential modifiers on breast cancer risk. Carcinogenesis. 2006; 27(9): 1876-1882.
- Steck SE, Gammon MD, Hebert JR, Wall DE, Zeisel SH. GSTM1, GSTT1, GSTP1, and GSTA1 Polymorphisms and Urinary Isothiocyanate Metabolites following Broccoli Consumption in Humans. J Nutr. 2007; 137: 904-909.
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- USDA. USDA Table of Nutrient Retention Factors, Release 5 (2003). http://www.nal.usda gov/fnic/foodcomp/Data/retn5/retn5_tbl.pdf. Accessed April 17, 2007.
This article appeared in Wise Traditions in Food, Farming and the Healing Arts, the quarterly magazine of the Weston A. Price Foundation, Summer 2007.