Supplementing with Veggies’ Best ConstituentsFighting Prostate Cancer
with Broccoli Compounds
Dietary indoles found in cruciferous vegetables
are beneficial for both men and women
By Dr. Edward R. Rosick
t seems to be the prerogative of youth to think of advice given to them by their elders as generally useless and annoying. This is especially true when it comes to dietary choices—how vividly I recall my grandmother telling me that if I wanted to grow up big and strong, I needed to eat such distasteful foods (at least to my youthful sensibilities) as broccoli, cauliflower, and cabbage in the form of sauerkraut.
Looking back (and going through my own battles to get my children to eat a semi-healthy diet), I sometimes wonder why my grandparents thought the way they did. What was passed down, generation after generation, that made them know almost instinctively that cruciferous vegetables, such as broccoli, cauliflower, cabbage, kale, and Brussels sprouts, are important for good health?
I3C causes cell death in breast
cancer cells but not in
noncancerous breast cells.
Although my grandparents are sadly no longer around to answer that question, there is now an impressive body of data showing that certain chemical compounds in cruciferous vegetables can protect men from prostate cancer, the second leading cause of cancer death among American men. This is but one example illustrating the age-old wisdom that eating a well-balanced diet full of fruits and vegetables is good for us. Let’s look at some of the evidence.
Cruciferous Vegetables Reduce Risk of
Two large studies published in 2000 showed that men who had a diet high in cruciferous vegetables had a statistically significant reduction in the risk of prostate cancer. In one of these studies, there was a remarkable 41% risk reduction among men who ate three or more servings of cruciferous vegetables per week, as compared to men eating fewer than one serving per week, even after the researchers controlled for all other vegetable intake. This led the researchers to conclude that “. . . the substitution of cruciferous vegetables for other vegetables, while keeping total vegetable intake constant, significantly reduces prostate cancer risk.”
Clearly, cruciferous veggies should make regular appearances on the dinner plates not only of children who want to grow up big and strong, but also of their fathers and grandfathers—and of their mothers and grandmothers too. Studies have shown that women who have diets high in cruciferous vegetables have a reduced risk of developing breast cancer.
I3C May Fight Breast and Cervical Cancer
It is now thought that one of the principal cancer-fighting constituents of cruciferous vegetables is a compound called indole-3-carbinol, or I3C for short. Two other compounds that also contribute a potent punch are very closely related to I3C. One is 3,3’-diindolylmethane (DIM), which is a dimer of I3C (i.e., two I3C molecules joined by a chemical bond), and the other is ascorbigen, which is an I3C molecule joined by a chemical bond to a molecule of vitamin C (ascorbic acid). Collectively, these three compounds are called dietary indoles (an indole being a certain type of organic compound).
I3C can inhibit the replication of
human papilloma virus, a
known cause of cervical cancer.
In animal studies examining chemically induced mammary tumors, all three of these compounds have been shown to reduce the number of tumors per animal. More recent work has shown that I3C causes cell death in breast cancer cells but not in noncancerous breast cells. Yet other studies on cell cultures have shown that I3C can inhibit the replication of human papilloma virus, a known cause of cervical cancer.
Estrogens: The Good and the Bad
Although the manner in which the dietary indoles protect against cancer is not entirely clear, a possible mechanism involves their actions on the hormone estrogen (which is actually not just one compound, but several related ones that have similar biological activities). Estrogen, which gives women their secondary sex characteristics, has only recently been discovered to be important in a number of physiological functions in men as well, including maintenance of bone mass and cognitive functions.
In women the majority of estrogen is produced by the ovaries, whereas in men it is produced primarily through the chemical conversion of androgenic (male) hormones by aromatase, an enzyme found in epithelial, fat, bone, and brain cells. Although some estrogen is essential to health in men (just as some testosterone is essential to health in women), too much of it can be harmful in both men and women, especially when it’s in the form of 16-alpha-hydroxyestrone. This compound, a product of estrogen metabolism, has high estrogenic activity and has been implicated in breast and cervical cancers (it’s called “bad estrogen”). A related estrogen metabolite, 2-hydroxyestrone, has low estrogenic activity and is believed to be much less harmful (it’s called “good estrogen”). Thus, the higher the ratio of 2-hydroxyestrone to 16-alpha-hydroxyestrone, the better.
Does Estrogen Cause Prostate Cancer?
Ask almost any mainstream physician what causes prostate cancer, and chances are the answer will be testosterone. This is based on research showing that castration, either physically or through chemical means, slows (but does not cure) prostate cancer. However, a growing number of doctors and researchers believe that estrogen and its metabolites, notably 16-alpha-hydroxyestrone, may be a significant factor in the development of prostate cancer. This idea is based on the fact that, while testosterone levels are highest in young men, prostate cancer is a disease almost exclusively of older men, who have lower levels of testosterone but higher levels of estrogen than younger men.
A recent article in the World Journal of Urology sums up the estrogen/prostate cancer issue succinctly: “Estrogenic stimulation through estrogen receptor alpha in a milieu of decreasing androgens [testosterone] contributes significantly to the genesis of benign prostatic hyperplasia, prostate dysplasia, and prostate cancer.”
Dietary Indoles Improve the Estrogen Ratio
One of the ways in which I3C, DIM, ascorbigen, and other phytochemicals found in cruciferous vegetables may fight cancer is through their action on estrogen and its metabolites. Studies have demonstrated that I3C increases the amount of 2-hydroxyestrone relative to the amount of 16-alpha-hydroxyestrone, thereby increasing the ratio of “good estrogen” to “bad estrogen”—a very good thing for both men and women.
For men, this could mean a decrease in the risk of prostate cancer. In a recent study that examined the association of this risk with estrogen metabolism, the authors stated that “Results of this case-control study suggest that the estrogen metabolic pathway favoring 2-hydroxylation over 16-alpha-hydroxylation may reduce the risk of clinically evident prostate cancer.” (Hydroxylation is the chemical process that leads to the estrogen metabolites in question.)
Dietary Indoles Kill Prostate Cancer Cells
With earlier work showing the effectiveness of I3C in preventing animal tumors, along with epidemiological studies showing that men who have a diet high in cruciferous vegetables have a decreased risk of prostate cancer, scientists are now examining the cellular mechanisms by which dietary indoles protect against prostate cancer.
In one such study, researchers exposed human prostate cancer cells to either I3C or DIM for 48 hours to examine their effects on cell proliferation. The researchers also studied the effects of I3C and DIM on the induction of apoptosis (cell death) in these cells. Both results were encouraging: the proliferation of prostate cancer cells was significantly reduced when they were exposed to I3C or DIM, and both of these agents caused apoptosis of the cells.
A similar study looked at the effects of using I3C as an adjunct to prostate cancer therapy with a substance called (get ready for this) tumor necrosis factor-related apoptosis-inducing ligand, mercifully known as TRAIL for short. TRAIL is a low-toxicity anticancer drug that has shown promise in inducing apoptosis in prostate cancer cells. It was found that I3C, even at very low doses, potentiated the prostate cancer-killing ability of TRAIL.
Dietary Indoles Are Well Tolerated
Although eating cruciferous vegetables regularly is fine and healthy,* it is not always possible—or it’s just plain inconvenient—to get the optimal amounts of the dietary indoles in this way. The answer to that, of course, is supplementation, but it behooves us to know the long-term effects of taking these compounds on a daily basis.
A recent study looked at the effects of high doses of I3C and DIM in rats over 3-month and 12-month periods. The results were encouraging: even though the animals were given the equivalent of seven times (in the case of I3C) to ten times (in the case of DIM) the recommended daily doses of these supplements for humans, there were no significant differences in blood chemistry between the animals in the 3-month and 12-month groups, leading the authors to conclude that “The data from this study confirm results from short-term studies indicating that both I3C and DIM are relatively nontoxic compounds.”
Dietary Indole Supplements Are the Way to Go
It’s wise to remember that laboratory and animal studies such as the ones discussed in this article are no substitute for clinical trials and cannot be regarded as the final word on the effects of the dietary indoles in humans. They do, however, provide a growing basis for confidence that these compounds are safe, nontoxic substances that may very well provide significant protection against prostate, breast, and cervical cancers.
Although the admonishment to “eat your veggies” is right on the money, especially where the cruciferous vegetables are concerned, the most reliable way to get the benefits of these highly healthful foods is in the convenient form of dietary indole supplements, which can help you optimize that important estrogen ratio we talked about.
- Cohen JH, Kristal AR, Stanford JL. Fruit and vegetable intakes and prostate cancer risk. J Natl Cancer Inst 2000;92(1):61-8.
- Kolonel LN et al. Vegetables, fruits, legumes, and prostate cancer: a multiethnic case-control study. Cancer Epidemiol Biomark Prev 2000;9:
- Freudenheim JL et al. Premenopausal breast cancer risk and intake of vegetables, fruits, and related nutrients. J Natl Cancer Inst 1996;88:340-8.
- PDR for Nutritional Supplements, Medical Economics Co., Montvale, NJ, 2001, pp 218-20.
- Rahman KMW, Aranha O, Sarkar FH. Indole-3-carbinol (I3C) induces apoptosis in tumorigenic but not in nontumorigenic breast epithelial cells. Nutr Cancer 2003;45(1):101-12.
- Nelson LR, Bulun SE. Estrogen production and action. J Am Acad Derm 2001;45(3):116-24.
- Steiner MS, Raghow S. Antiestrogens and selective estrogen receptor modulators reduce prostate cancer risk. World J Urol 2003;21(1):31-6.
- Muti P et al. Urinary estrogen metabolites and prostate cancer: a case-control study in the United States. Cancer Causes Control 2002;13(10):
- Nachshon-Kedmi M, Yannai S, Haj A, Fares FA. Indole-3-carbinol and 3,3’-diindolylmethane induce apoptosis in human prostate cancer cells. Food Chem Toxicol 2003;41:745-52.
- Jeon K-I et al. Pretreatment of indole-3-carbinol augments TRAIL-induced apoptosis in a prostate cancer cell line, LNCaP. FEBS Lett 2003;544:246-51.
- Leibelt DA et al. Evaluation of chronic dietary exposure to indole-3-carbinol and absorption-enhanced 3,3’-diindolylmethane in Sprague-Dawley rats. Toxicol Sci 2003;74:10-21.
Dietary Indoles for Fibromyalgia
Fibromyalgia (the word means “fibrous-tissue muscle pain”) is a complex syndrome that affects millions of people (mostly women) worldwide. First described in the early 1800s, this condition has been called by various names, including muscular rheumatism, neurasthenia, and fibrositis (a misnomer because it implies an inflammation, which is lacking in fibromyalgia). The symptoms include muscle pain, nonrestorative sleep, fatigue, and multiple tender points scattered over the body.
There is not yet a recognized treatment for people who suffer from this debilitating disease, but studies are being conducted on supplements that may help relieve some of its more troublesome symptoms. One such supplement is ascorbigen.
In a small, open-label (not blinded) study, researchers recently tested a supplement consisting of 100 mg of ascorbigen and 400 mg of broccoli powder per day on 12 women, aged 29 to 52, who had been diagnosed with fibromyalgia. The researchers’ objectives were: (1) measurement of 18 tender-point pain threshold levels and (2) assessment of the physical impairment and total impact scores as measured by the Fibromyalgia Impact Questionnaire (FIQ). The latter took into account the patients’ physical functioning, work difficulty, pain, fatigue, morning tiredness, stiffness, anxiety, and depression.
The patients’ condition was evaluated at the start of the study and then 28–30 days after they had been taking one capsule per day of the ascorbigen/broccoli powder mix. By that time, there was a 9.1% increase (desirable) in the group’s mean tender-point pain threshold level and decreases (also desirable) in the FIQ scores: 19.7% in physical impairment and 17.8% in total impact.
Although gratifying, these results are highly preliminary and cannot be seen as good evidence of a positive effect of ascorbigen. The authors themselves concluded that “Due to the small number of participants and the open-label design of this study, we cannot rule out a placebo effect as a mechanism of the positive changes seen.” Thus, although treating fibromyalgia is not something ascorbigen or other dietary indoles can yet lay claim to, it’s encouraging that the possibility exists.
- Bramwell B, Ferguson S, Scarlett N, Macintosh A. The use of ascorbigen in the treatment of fibromyalgia patients: a preliminary trial. Altern Med Rev 2000;5(5):455-62.
Dr. Rosick is an attending physician and clinical assistant professor of medicine at Pennsylvania State University, where he specializes in preventive and alternative medicine. He also holds a master’s degree in healthcare administration.