Research: Yes, Diet Has a Huge Role In Health
Last week The New York Times printed an article featuring a study claiming that a low-fat diet does little to prevent cancer and heart disease. Dr. Fuhrman responded with ten reasons to keep eating healthy food despite the headlines.
Today New York Times reporter Gina Kolata continues to further the notion that what you eat might not shape your medical fate:
It's one of the great principles — no, more than principles, canons — of American culture to suggest that what you eat affects your health.Her article cites the rise and fall of numerous fad diets. Dr. David Altshuler, an endocrinologist and geneticist at Massachusetts General Hospital is quoted urging caution when making dietary suggestions:
It's this idea that you control your own destiny and that it's never too late to reinvent yourself. Vice gets punished and virtue gets rewarded. If you eat or drink or inhale the wrong things you get sick. If not, you get healthy. Says James Morone, a professor of political science at Brown University.
We should limit strong advice to where randomized trials have proven a benefit of lifestyle modification.Of course, fad diets have never been the answer. And health care professionals should be exceedingly careful in what they recommend--because a lot of common assumptions about food are not supported by science. (T. Colin Campbell's revolutionary research showing the dangers of too much animal protein was born out of his conviction that getting more animal protein to the malnourished of the developing world was the key to good health--instead he found that reducing animal protein in his own diet was the biggest lesson.)
But if you look at the science, there is not a serious case to be made that diet is not tied to health. Just as there are studies showing smoking is not good for you, so are there studies showing certain foods are not good for you, while others can play a huge role in combating chronic disease.
Dr. Fuhrman's dietary recommendations are based on many thousands of studies. Click "continue reading" to see references and summaries to 19 of them that, together, should go a long way to convincing anyone that yes, it does matter what you eat.
Jenkins DJ, Kendall CW, Popovich DG, et al. Effect of a very-high-fiber vegetable, fruit, and nut diet on serum lipids and colonic function. Metabolism 2001 Apr;50(4):494-503.
We tested the effects of feeding a diet very high in fiber from fruit and vegetables. The levels fed were those, which had originally inspired the dietary fiber hypothesis related to colon cancer and heart disease prevention and also may have been eaten early in human evolution. Ten healthy volunteers each took 3 metabolic diets of 2 weeks duration. The diets were: high-vegetable, fruit, and nut (very-high-fiber, 55 g/1,000 kcal); starch-based containing cereals and legumes (early agricultural diet); or low-fat (contemporary therapeutic diet). All diets were intended to be weight-maintaining (mean intake, 2,577 kcal/d). Compared with the starch-based and low-fat diets, the high-fiber vegetable diet resulted in the largest reduction in low-density lipoprotein (LDL) cholesterol (33% +/- 4%, P <.001) and the greatest fecal bile acid output (1.13 +/- 0.30 g/d, P =.002), fecal bulk (906 +/- 130 g/d, P <.001), and fecal short-chain fatty acid outputs (78 +/- 13 mmol/d, P <.001). Nevertheless, due to the increase in fecal bulk, the actual concentrations of fecal bile acids were lowest on the vegetable diet (1.2 mg/g wet weight, P =.002). Maximum lipid reductions occurred within 1 week. Urinary mevalonic acid excretion increased (P =.036) on the high-vegetable diet reflecting large fecal steroid losses. We conclude that very high-vegetable fiber intakes reduce risk factors for cardiovascular disease and possibly colon cancer. Vegetable and fruit fibers therefore warrant further detailed investigation.
Jenkins DJ, Kendall CW, Marchie A, et al. The Garden of Eden--plant based diets, the genetic drive to conserve cholesterol and its implications for heart disease in the 21st century. Comp Biochem Physiol A Mol Integr Physiol 2003 Sep;136(1):141-151.
It is likely that plant food consumption throughout much of human evolution shaped the dietary requirements of contemporary humans. Diets would have been high in dietary fiber, vegetable protein, plant sterols and associated phytochemicals, and low in saturated and trans-fatty acids and other substrates for cholesterol biosynthesis. To meet the body's needs for cholesterol, we believe genetic differences and polymorphisms were conserved by evolution, which tended to raise serum cholesterol levels. As a result modern man, with a radically different diet and lifestyle, especially in middle age, is now recommended to take medications to lower cholesterol and reduce the risk of cardiovascular disease. Experimental introduction of high intakes of viscous fibers, vegetable proteins and plant sterols in the form of a possible Myocene diet of leafy vegetables, fruit and nuts, lowered serum LDL-cholesterol in healthy volunteers by over 30%, equivalent to first generation statins, the standard cholesterol-lowering medications. Furthermore, supplementation of a modern therapeutic diet in hyperlipidemic subjects with the same components taken as oat, barley and psyllium for viscous fibers, soy and almonds for vegetable proteins and plant sterol-enriched margarine produced similar reductions in LDL-cholesterol as the Myocene-like diet and reduced the majority of subjects' blood lipids concentrations into the normal range. We conclude that reintroduction of plant food components, which would have been present in large quantities in the plant based diets eaten throughout most of human evolution into modern diets can correct the lipid abnormalities associated with contemporary eating patterns and reduce the need for pharmacological interventions
Hu FB. Plant-based foods and prevention of cardiovascular disease: an overview. Am J Clin Nutr 2003 Sep;78(3 Suppl):544S-551S.
Evidence from prospective cohort studies indicates that a high consumption of plant-based foods such as fruit and vegetables, nuts, and whole grains is associated with a significantly lower risk of coronary artery disease and stroke. The protective effects of these foods are probably mediated through multiple beneficial nutrients contained in these foods, including mono- and polyunsaturated fatty acids, n-3 fatty acids, antioxidant vitamins, minerals, phytochemicals, fiber, and plant protein. In dietary practice, healthy plant-based diets do not necessarily have to be low in fat. Instead, these diets should include unsaturated fats as the predominant form of dietary fat (eg, fats from natural liquid vegetable oils and nuts), whole grains as the main form of carbohydrate, an abundance of fruit and vegetables, and adequate n-3 fatty acids. Such diets, which also have many other health benefits, deserve more emphasis in dietary recommendations to prevent chronic diseases.
He K, Hu FB, Colditz GA, et al. Changes in intake of fruits and vegetables in relation to risk of obesity and weight gain among middle-aged women. Int J Obes Relat Metab Disord 2004 Dec;28(12):1569-1574.
OBJECTIVE: To examine the changes in intake of fruits and vegetables in relation to risk of obesity and weight gain among middle-aged women. DESIGN: Prospective cohort study with 12 y of follow-up conducted in the Nurses' Health Study. SUBJECTS: A total of 74,063 female nurses aged 38-63 y, who were free of cardiovascular disease, cancer, and diabetes at baseline in 1984. MEASUREMENTS: Dietary information was collected using a validated food frequency questionnaire, and body weight and height were self-reported. RESULTS: During the 12-y follow-up, participants tended to gain weight with aging, but those with the largest increase in fruit and vegetable intake had a 24% of lower risk of becoming obese (BMI> or =30 kg/m2) compared with those who had the largest decrease in intake after adjustment for age, physical activity, smoking, total energy intake, and other lifestyle variables (relative risk (RR), 0.76; 95% confidence interval (CI), 0.69-0.86; P for trend <0.0001). For major weight gain (> or =25 kg), women with the largest increase in intake of fruits and vegetables had a 28% lower risk compared to those in the other extreme group (RR, 0.72; 95% CI, 0.55-0.93; P=0.01). Similar results were observed for changes in intake of fruits and vegetables when analyzed separately. CONCLUSIONS: Our findings suggest that increasing intake of fruits and vegetables may reduce long-term risk of obesity and weight gain among middle-aged women.
Hu FB, Willett WC. Optimal diets for prevention of coronary heart disease. JAMA 2002 Nov 27;288(20):2569-2578.
CONTEXT: Coronary heart disease (CHD) remains the leading cause of mortality in industrialized countries and is rapidly becoming a primary cause of death worldwide. Thus, identification of the dietary changes that most effectively prevent CHD is critical. OBJECTIVE: To review metabolic, epidemiologic, and clinical trial evidence regarding diet and CHD prevention. DATA SOURCES AND STUDY SELECTION: We searched MEDLINE through May 2002 for epidemiologic and clinical investigations of major dietary factors (fat, cholesterol, omega-3 fatty acids, trans-fatty acids, carbohydrates, glycemic index, fiber, folate, specific foods, and dietary patterns) and CHD. We selected 147 original investigations and reviews of metabolic studies, epidemiologic studies, and dietary intervention trials of diet and CHD. DATA EXTRACTION: Data were examined for relevance and quality and extracted by 1 of the authors. DATA SYNTHESIS: Compelling evidence from metabolic studies, prospective cohort studies, and clinical trials in the past several decades indicates that at least 3 dietary strategies are effective in preventing CHD: substitute nonhydrogenated unsaturated fats for saturated and trans-fats; increase consumption of omega-3 fatty acids from fish, fish oil supplements, or plant sources; and consume a diet high in fruits, vegetables, nuts, and whole grains and low in refined grain products. However, simply lowering the percentage of energy from total fat in the diet is unlikely to improve lipid profile or reduce CHD incidence. Many issues remain unsettled, including the optimal amounts of monounsaturated and polyunsaturated fats, the optimal balance between omega-3 and omega-6 polyunsaturated fats, the amount and sources of protein, and the effects of individual phytochemicals, antioxidant vitamins, and minerals. CONCLUSIONS: Substantial evidence indicates that diets using nonhydrogenated unsaturated fats as the predominant form of dietary fat, whole grains as the main form of carbohydrates, an abundance of fruits and vegetables, and adequate omega-3 fatty acids can offer significant protection against CHD. Such diets, together with regular physical activity, avoidance of smoking, and maintenance of a healthy body weight, may prevent the majority of cardiovascular disease in Western populations.
Hu FB, Stampfer MJ. Nut consumption and risk of coronary heart disease: a review of epidemiologic evidence. Curr Atheroscler Rep 1999 Nov;1(3):204-209.
Traditionally nuts have been perceived as an unhealthy food because of their high fat content. However, recent accumulative evidence suggests that frequent consumption of nuts may be protective against coronary heart disease (CHD). So far, five large prospective cohort studies (the Adventist Health Study, the Iowa Women Health Study, the Nurses' Health Study, the Physicians' Health Study, and the CARE Study) have examined the relation between nut consumption and the risk of CHD and all have found an inverse association. In addition, several clinical studies have observed beneficial effects of diets high in nuts (including walnuts, peanuts, almonds, and other nuts) on blood lipids. The beneficial effects of nut consumption observed in clinical and epidemiologic studies underscore the importance of distinguishing different types of fat. Most fats in nuts are mono- and polyunsaturated fats that lower low-density lipoprotein cholesterol level. Based on the data from the Nurses' Health Study, we estimated that substitution of the fat from 1 ounce of nuts for equivalent energy from carbohydrate in an average diet was associated with a 30% reduction in CHD risk and the substitution of nut fat for saturated fat was associated with 45% reduction in risk. Given the strong scientific evidence for the beneficial effects of nuts, it seems justifiable to move nuts to a more prominent place in the United States Department of Agriculture Food Guide Pyramid. Regular nut consumption can be recommended in the context of a healthy and balanced diet.
Campbell TC, Parpia B, Chen J. Diet, lifestyle, and the etiology of coronary artery disease: the Cornell China study. Am J Cardiol 1998 Nov 26;82(10B):18T-21T
Investigators collected and analyzed mortality data for >50 diseases, including 7 different cancers, from 65 counties and 130 villages in rural mainland China. Blood, urine, food samples, and detailed dietary data were collected from 50 adults in each village and analyzed for a variety of nutritional, viral, hormonal, and toxic chemical factors. In rural China, fat intake was less than half that in the United States, and fiber intake was 3 times higher. Animal protein intake was very low, only about 10% of the US intake. Mean serum total cholesterol was 127 mg/dL in rural China versus 203 mg/dL for adults aged 20-74 years in the United States. Coronary artery disease mortality was 16.7-fold greater for US men and 5.6-fold greater for US women than for their Chinese counterparts. The combined coronary artery disease mortality rates for both genders in rural China were inversely associated with the frequency of intake of green vegetables and plasma erythrocyte monounsaturated fatty acids, but positively associated with a combined index of salt intake plus urinary sodium and plasma apolipoprotein B. These apolipoproteins, in turn, are positively associated with animal protein intake and the frequency of meat intake and inversely associated with plant protein, legume, and light-colored vegetable intake. Rates of other diseases were also correlated with dietary factors. There was no evidence of a threshold beyond which further benefits did not accrue with increasing proportions of plant-based foods in the diet.
Campbell TC, Junshi C. Diet and chronic degenerative diseases: perspectives from China. Am J Clin Nutr 1994 May;59(5 Suppl):1153S-1161S.
A comprehensive ecologic survey of dietary, life-style, and mortality characteristics of 65 counties in rural China showed that diets are substantially richer in foods of plant origin when compared with diets consumed in the more industrialized, Western societies. Mean intakes of animal protein (about one-tenth of the mean intake in the United States as energy percent), total fat (14.5% of energy), and dietary fiber (33.3 g/d) reflected a substantial preference for foods of plant origin. Mean plasma cholesterol concentration, at approximately 3.23-3.49 mmol/L, corresponds to this dietary life-style. The principal hypothesis under investigation in this paper is that chronic degenerative diseases are prevented by an aggregate effect of nutrients and nutrient-intake amounts that are commonly supplied by foods of plant origin. The breadth and consistency of evidence for this hypothesis was investigated with multiple intake-biomarker-disease associations, which were appropriately adjusted. There appears to be no threshold of plant-food enrichment or minimization of fat intake beyond which further disease prevention does not occur. These findings suggest that even small intakes of foods of animal origin are associated with significant increases in plasma cholesterol concentrations, which are associated, in turn, with significant increases in chronic degenerative disease mortality rates.
Esselstyn CB, Ellis SG, Medendorp SV, Crowe TD. A strategy to arrest and reverse coronary artery disease: a 5-year longitudinal study of a single physician's practice. J Fam Pract 1995 Dec;41(6):560-568.
BACKGROUND. Animal experiments and epidemiological studies have suggested that coronary disease could be prevented, arrested, or even reversed by maintaining total serum cholesterol levels below 150 mg/dL (3.88 mmol/L). In 1985, we began to study how effective one physician could be in helping patients achieve this cholesterol level and what the associated effect of achieving and maintaining this cholesterol level has on coronary disease. METHODS. The study included 22 patients with angiographically documented, severe coronary artery disease that was not immediately life threatening. These patients took cholesterol-lowering drugs and followed a diet that derived no more than 10% of its calories from fat. Disease progression was measured by coronary angiography and quantified with the percent diameter stenosis and minimal lumen diameter methods. Serum cholesterol was measured biweekly for 5 years and monthly thereafter. RESULTS. Of the 22 participants, 5 dropped out within 2 years, and 17 maintained the diet, 11 of whom completed a mean of 5.5 years of follow-up. All 11 of these participants reduced their cholesterol level from a mean baseline of 246 mg/dL (6.36 mmol/L) to below 150 mg/dL (3.88 mmol/L). Lesion analysis by percent stenosis showed that of 25 lesions, 11 regressed and 14 remained stable. Mean arterial stenosis decreased from 53.4% to 46.2% (estimated decrease = 7%; 95% confidence interval [CI], 3.3 to 10.7, P < .05). Analysis by minimal lumen diameter of 25 lesions found that 6 regressed, 14 remained stable, and 5 progressed. Mean lumen diameter increased from 1.3 mm to 1.4 mm (estimated increase = 0.08 mm; 95% CI, -0.06 to 0.22, P = NS). Disease was clinically arrested in all 11 participants, and none had new infarctions. Among the 11 remaining patients after 10 years, six continued the diet and had no further coronary events, whereas the five dropouts who resumed their prestudy diet reported 10 coronary events. CONCLUSIONS. A physician can influence patients in the decision to adopt a very low-fat diet that, combined with lipid-lowering drugs, can reduce cholesterol levels to below 150 mg/dL and uniformly result in the arrest or reversal of coronary artery disease.
Esselstyn CB. In cholesterol lowering, moderation kills. Cleve Clin J Med 2000 Aug;67(8):560-564. Esselstyn CB. Updating a 12-year experience with arrest and reversal therapy for coronary heart disease (an overdue requiem for palliative cardiology). Am J Cardiol 1999 Aug 1;84(3):339-341, A8
The high-fat American diet is responsible for an epidemic of coronary artery disease. A plant-based diet with less than 10% fat will prevent coronary disease from developing, halt the progress of existing disease, and even reverse the disease in many patients. Given proper support and education, motivated patients with a history of coronary disease can follow this diet and prevent future cardiac events. (Second Paper) Coronary artery disease is essentially nonexistent in cultures whose nutrition assures cholesterol levels <150 mg/dl. Patients with advanced coronary artery disease may abolish disease progression through a plant-based diet and cholesterol-lowering medication to achieve and maintain a total cholesterol <150 mg/dl.
Esselstyn CB. Resolving the Coronary Artery Disease Epidemic Through Plant-Based Nutrition. 2001 Autumn;4(4):171-177
The world's advanced countries have easy access to plentiful high-fat food; ironically, it is this rich diet that produces atherosclerosis. In the world's poorer nations, many people subsist on a primarily plant-based diet, which is far healthier, especially in terms of heart disease. To treat coronary heart disease, a century of scientific investigation has produced a device-driven, risk factor-oriented strategy. Nevertheless, many patients treated with this approach experience progressive disability and death. This strategy is a rear-guard defensive one. In contrast, compelling data from nutritional studies, population surveys, and interventional studies support the effectiveness of a plant-based diet and aggressive lipid lowering to arrest, prevent, and selectively reverse heart disease. In essence, this is an offensive strategy. The single biggest step toward adopting this strategy would be to have United States dietary guidelines support a plant-based diet. An expert committee purged of industrial and political influence is required to assure that science is the basis for dietary recommendations.
Shannon J, Ray R, Wu C, Nelson Z. Food and botanical groupings and risk of breast cancer: a case-control study in Shanghai, China. Cancer Epidemiol Biomarkers Prev 2005 Jan;14(1):81-90.
Breast cancer incidence rates more than double in Chinese women as they migrate from China to Hong Kong to the United States, suggesting that environmental factors contribute to the international variation in breast cancer incidence. Several dietary factors, which differ between the United States and the Chinese population, including intake of soy, meat, and fruits and vegetables, have been suggested to affect breast cancer risk. This report describes results from a case-control study of diet and risk of breast cancer nested in a randomized trial of breast self exam in Shanghai, China. Participating breast cancer cases (n = 378) and frequency age-matched controls (n = 1,070) completed a comprehensive food frequency questionnaire and a risk factor questionnaire. After adjustment for age, total energy intake, and total years of breast-feeding, women in the highest quartile of fruit and vegetable intake (> or =3.8 servings/d) were significantly less likely to have breast cancer (odds ratio, 0.48; 95% confidence interval, 0.29-0.78) as compared with women in the lowest quartile of intake ( < or =2.3 servings/d). Egg consumption was also significantly inversely associated with risk of breast cancer (odds ratio for > or =6.0 eggs/wk versus < or =2.0 eggs/wk is 0.56; 95% confidence interval, 0.35-0.91). There was no difference in soy consumption between cases and controls. None of the associations with a single botanical family explained the strong inverse relationship between fruits and vegetables and breast cancer risk. These results provide additional evidence in support of the important role of fruits and vegetables in breast cancer prevention.
Cho E, Spiegelman D, Hunter DJ, et al. Premenopausal fat intake and risk of breast cancer. J Natl Cancer Inst (United States), Jul 16 2003, 95(14) p1079-1085.
BACKGROUND: International comparisons and case-control studies have suggested a positive relation between dietary fat intake and breast cancer risk, but prospective studies, most of them involving postmenopausal women, have not supported this association. We conducted a prospective analysis of the relation between dietary fat intake and breast cancer risk among premenopausal women enrolled in the Nurses' Health Study II. METHODS: Dietary fat intake and breast cancer risk were assessed among 90 655 premenopausal women aged 26 to 46 years in 1991. Fat intake was assessed with a food-frequency questionnaire at baseline in 1991 and again in 1995. Breast cancers were self-reported and confirmed by review of pathology reports. Multivariable relative risks (RRs) and 95% confidence intervals (CIs) were calculated. All statistical tests were two-sided. RESULTS: During 8 years of follow-up, 714 women developed incident invasive breast cancer. Relative to women in the lowest quintile of fat intake, women in the highest quintile of intake had a slight increased risk of breast cancer (RR = 1.25, 95% CI = 0.98 to 1.59; P(trend) =.06). The increase was associated with intake of animal fat but not vegetable fat; RRs for the increasing quintiles of animal fat intake were 1.00 (referent), 1.28, 1.37, 1.54, and 1.33 (95% CI = 1.02 to 1.73; P(trend) =.002). Intakes of both saturated and monounsaturated fat were related to modestly elevated breast cancer risk. Among food groups contributing to animal fat, red meat and high-fat dairy foods were each associated with an increased risk of breast cancer. CONCLUSIONS: Intake of animal fat, mainly from red meat and high-fat dairy foods, during premenopausal years is associated with an increased risk of breast cancer.
Steinmetz KA, Potter JD. Vegetables, fruit, and cancer prevention: a review. J Am Diet Assoc 1996 Oct;96(10):1027-1039.
In this review of the scientific literature on the relationship between vegetable and fruit consumption and risk of cancer, results from 206 human epidemiologic studies and 22 animal studies are summarized. The evidence for a protective effect of greater vegetable and fruit consumption is consistent for cancers of the stomach, esophagus, lung, oral cavity and pharynx, endometrium, pancreas, and colon. The types of vegetables or fruit that most often appear to be protective against cancer are raw vegetables, followed by allium vegetables, carrots, green vegetables, cruciferous vegetables, and tomatoes. Substances present in vegetables and fruit that may help protect against cancer, and their mechanisms, are also briefly reviewed; these include dithiolthiones, isothiocyanates, indole-3-carbinol, allium compounds, isoflavones, protease inhibitors, saponins, phytosterols, inositol hexaphosphate, vitamin C, D-limonene, lutein, folic acid, beta carotene, lycopene, selenium, vitamin E, flavonoids, and dietary fiber. Current US vegetable and fruit intake, which averages about 3.4 servings per day, is discussed, as are possible noncancer-related effects of increased vegetable and fruit consumption, including benefits against cardiovascular disease, diabetes, stroke, obesity, diverticulosis, and cataracts. Suggestions for dietitians to use in counseling persons toward increasing vegetable and fruit intake are presented.
Rose P, Huang Q, Ong CN, Whiteman M. Broccoli and watercress suppress matrix metalloproteinase-9 activity and invasiveness of human MDA-MB-231 breast cancer cells. Toxicol Appl Pharmacol 2005 Jun 10; pS0041-008X
A high dietary intake of cruciferous vegetables has been associated with a reduction in numerous human pathologies particularly cancer. In the current study, we examined the inhibitory effects of broccoli (Brassica oleracea var. italica) and watercress (Rorripa nasturtium aquaticum) extracts on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced cancer cell invasion and matrix metalloproteinase-9 activity using human MDA-MB-231 breast cancer cells. Aberrant overexpression of matrix metalloproteinases, including metalloproteinase-9, is associated with increased invasive potential in cancer cell lines. Our results demonstrate that extracts of broccoli and Rorripa suppressed TPA-induced MMP-9 activity and invasiveness in a concentration dependant manner as determined by zymographic analysis. Furthermore, fractionation of individual extracts followed by liquid chromatography mass spectroscopy analysis (LC-MS) revealed that the inhibitory effects of each vegetable were associated with the presence of 4-methysulfinylbutyl (sulforaphane) and 7-methylsulphinylheptyl isothiocyanates. Taken together, our data indicate that isothiocyanates derived form broccoli and Rorripa inhibit metalloproteinase 9 activities and also suppress the invasive potential of human MDA-MB-231 breast cancer cells in vitro. The inhibitory effects observed in the current study may contribute to the suppression of carcinogenesis by diets high in cruciferous vegetables.
Johnston N. Sulforaphane halts breast cancer cell growth. Drug Discov Today 2004 Nov 1;9(21):908.
Sulforaphane is a chemical found in cruciferous vegetables such as broccoli, sprouts and kale. This compound is a potent inducer of protective enzymes that provide defense against cancer-causing chemicals. Researchers have discovered that sulforaphane can halt human breast cancer cells in their tracks and have identified a new mechanism of action for the compound.
Srivastava SK, Xiao D, Lew KL, et al. Allyl isothiocyanate, a constituent of cruciferous vegetables, inhibits growth of PC-3 human prostate cancer xenografts in vivo. Carcinogenesis 2003 Oct;24(10):1665-1670.
We have shown previously that allyl isothiocyanate (AITC), a constituent of cruciferous vegetables, significantly inhibits survival of PC-3 and LNCaP human prostate cancer cells in culture, whereas proliferation of a normal prostate epithelial cell line is minimally affected by AITC even at concentrations that are highly cytotoxic to the prostate cancer cells. The present studies were designed to test the hypothesis that AITC administration may retard growth of human prostate cancer xenografts in vivo. Bolus i.p. injection of 10 micromol AITC, three times per week (Monday, Wednesday and Friday) beginning the day of tumor cell implantation, significantly inhibited the growth of PC-3 xenograft (P < 0.05 by two-way ANOVA). For example, 26 days after tumor cell implantation, the average tumor volume in control mice (1025 +/- 205 mm3) was approximately 1.7-fold higher compared with AITC-treated mice. Histological analysis of tumors excised at the termination of the experiment revealed a statistically significant increase in number of apoptotic bodies with a concomitant decrease in cells undergoing mitosis in the tumors of AITC-treated mice compared with that of control mice. Western blot analysis indicated an approximately 70% reduction in the levels of anti-apoptotic protein Bcl-2 in the tumor lysate of AITC-treated mice compared with that of control mice. Moreover, the tumors from AITC-treated mice, but not control mice, exhibited cleavage of BID, which is known to promote apoptosis. Statistically significant reduction in the expression of several proteins that regulate G2/M progression, including cyclin B1, cell division cycle (Cdc)25B and Cdc25C (44, 45 and 90% reduction, respectively, compared with control), was also observed in the tumors of AITC-treated mice relative to control tumors. In conclusion, the results of the present study indicate that AITC administration inhibits growth of PC-3 xenografts in vivo by inducing apoptosis and reducing mitotic activity.
Finley JW. The antioxidant responsive element (ARE) may explain the protective effects of cruciferous vegetables on cancer. Nutr Rev 2003 Jul;61(7):250-254.
Research supports the hypothesis that one's diet has a great impact on his or her risk of cancer. Many studies have found that increased fruit and vegetable intake decreases the risk of cancer. Cruciferous vegetables such as broccoli and cauliflower seem to be especially protective against cancer. Most studies show that phytochemicals in crucifers up-regulate many detoxification enzyme systems in the animal that consumes them. Recent reports of the molecular events involved in the activation of a gene promoter called the antioxidant responsive element have begun to provide clues as to how a single substance may induce a battery of many genes
Seow A, Yuan JM, Sun CL, et al. Dietary isothiocyanates, glutathione S-transferase polymorphisms and colorectal cancer risk in the Singapore Chinese Health Study. Carcinogenesis 2002 Dec;23(12):2055-2061
Dietary intake of cruciferous vegetables (Brassica spp.) has been inversely related to colorectal cancer risk, and this has been attributed to their high content of glucosinolate degradation products such as isothiocyanates (ITCs). These compounds act as anticarcinogens by inducing phase II conjugating enzymes, in particular glutathione S-transferases (GSTs). These enzymes also metabolize ITCs, such that the protective effect of cruciferous vegetables may predicate on GST genotype. The Singapore Chinese Health Study is a prospective investigation among 63 257 middle-aged men and women, who were enrolled between April 1993 and December 1998. In this nested case-control analysis, we compared 213 incident cases of colorectal cancer with 1194 controls. Information on dietary ITC intake from cruciferous vegetables, collected at recruitment via a semi-quantitative food frequency questionnaire, was combined with GSTM1, T1 and P1 genotype from peripheral blood lymphocytes or buccal mucosa. When categorized into high (greater than median) and low (less than/equal to median) intake, dietary ITC was slightly lower in cases than controls but the difference was not significant [odds ratio (OR) 0.81, 95% confidence interval (CI) 0.59-1.12]. There were no overall associations between GSTM1, T1 or P1 genotypes and colorectal cancer risk. However, among individuals with both GSTM1 and T1 null genotypes, we observed a 57% reduction in risk among high versus low consumers of ITC (OR 0.43, 95% CI 0.20-0.96), in particular for colon cancer (OR 0.31, 0.12-0.84). Our results are compatible with the hypothesis that ITCs from cruciferous vegetables modify risk of colorectal cancer in individuals with low GST activity. Further, this gene-diet interaction may be important in studies evaluating the effect of risk-enhancing compounds in the colorectum.