Gerd Bobe

Dietary Flavonoids and Colorectal Adenoma Recurrence in the Polyp Prevention Trial

Two recent case-control studies suggested that some flavonoid subgroups may play a role in preventing colorectal cancer. Previous prospective cohort studies generally reported no association; however, only a small subset of flavonoids was evaluated and partial flavonoid databases were used. We used the newly constructed U.S. Department of Agriculture flavonoid database to examine the association between consumption of total flavonoids, 6 flavonoid subgroups, and 29 individual flavonoids with adenomatous polyp recurrence in the Polyp Prevention Trial. The Polyp Prevention Trial was a randomized dietary intervention trial, which examined the effectiveness of a low-fat, high-fiber, high-fruit, and high-vegetable diet on adenoma recurrence. Intakes of flavonoids were estimated from a food frequency questionnaire. Multivariate logistic regression models (adjusted for age, body mass index, sex, regular non–steroidal anti-inflammatory use, and dietary fiber intake) were used to estimate odds ratios and 95% confidence intervals for both any and advanced adenoma recurrence within quartiles of energy-adjusted flavonoid intake (baseline, during the trial, and change during the trial). Total flavonoid intake was not associated with any or advanced adenoma recurrence. However, high intake of flavonols, which are at greater concentrations in beans, onions, apples, and tea, was associated with decreased risk of advanced adenoma recurrence (4th versus 1st quartile during the trial; odds ratio, 0.24; 95% confidence interval, 0.11, 0.53; Ptrend = 0.0006). Similar inverse associations were observed to a smaller extent for isoflavonoids, the flavonol kaempferol, and the isoflavonoids genistein and formononetin. Our data suggest that a flavonol-rich diet may decrease the risk of advanced adenoma recurrence. (Cancer Epidemiol Biomarkers Prev 2008;17(6):1344–53)

Consumption of a Legume-Enriched, Low-Glycemic Index Diet Is Associated with Biomarkers of Insulin Resistance and Inflammation among Men at Risk for Colorectal Cancer

The Legume Inflammation Feeding Experiment is, to our knowledge, the first randomized crossover feeding trial testing the effects of a legume-enriched, low-glycemic index (GI) diet among men characterized for colorectal adenomas and insulin resistance (IR) status. This study was designed to test the effects of a legume-enriched diet compared with a healthy American (HA) diet under weight-stable conditions. The primary objective was to assess effects on C-reactive protein (CRP) and C-peptide levels. The secondary objective was to assess changes by IR status or history of adenomas. A total of 64 men who completed a colonoscopy within the previous 2 y consumed 2 diets in random order each for 4 wk separated by a washout period. The diets were a legume-enriched (250 g/d), low-GI (GI 38) diet and a high-GI (GI 69) HA diet. We measured fasting glucose, insulin, C-peptide, CRP, and soluble tumor necrosis factor-alpha receptors I and II (sTNFRI/II) at the beginning and end of the diet periods. Participants who consumed both the legume and HA diets had favorably improved CRP (-20.2 and -18.3%) and sTNFRI (-3.7 and -4.4%) concentrations, respectively. The sTNFRII concentrations declined marginally during the legume diet period (-3.8%; P = 0.060) and significantly during the HA diet period (-5.1%; P < 0.001). Fasting glucose increased significantly during both the legume (+1.8%) and HA (-2.2%) diet periods. Only the changes in glucose differed between the diet periods. Serum C-peptide and plasma insulin levels did not change in participants consuming either diet. Healthful dietary changes can improve biomarkers of IR and inflammation.

Flavonoid consumption and esophageal cancer among black and white men in the United States

Flavonoids and proanthocyanidins are bioactive polyphenolic components of fruits and vegetables that may account for part of the protective effect of raw fruit and vegetable consumption in esophageal cancer. We studied the relationship between esophageal cancer and dietary proanthocyanidins, flavonoids and flavonoid subclasses (anthocyanidins, flavan‐3‐ols, flavanones, flavones, flavonols and isoflavonoids) using recently developed USDA and Tufts flavonoid and proanthocyanidin databases. The study was a population‐based, case–control analysis of 161 white men with esophageal adenocarcinoma (EAC), 114 white and 218 black men with esophageal squamous cell carcinoma (ESCC) and 678 white and 557 black male controls who lived in 3 areas of the United States. Neither total flavonoid nor proanthocyanidin intake was associated with EAC and ESCC in either white or black men. In white men, inverse associations were observed between anthocyanidin intake and EAC (4th vs. 1st quartile odds ratio [OR], 0.47, 95% confidence interval [CI], 0.24–0.91; ptrend = 0.04) and between isoflavonoid intake and ESCC (4th vs. 1st quartile OR, 0.43, 95% CI, 0.20–0.93; ptrend = 0.01). None of the associations remained significant after adjusting for dietary fiber, which is strongly correlated with flavonoid consumption. We conclude that total flavonoids and proanthocyanidins do not have strong protective effects in either EAC or ESCC. Some protective effects were evident in flavonoid subclasses and population subgroups. In white men, foods rich in anthocyanidins may have chemopreventive effects in EAC and those rich in isoflavonoids may do so in ESCC.

Dietary Cooked Navy Beans and Their Fractions Attenuate Colon Carcinogenesis in Azoxymethane-Induced Ob/Ob Mice

Based on the protective effects of cooked dry bean consumption in a human intervention study, we evaluated which fraction of cooked dry beans is responsible for its cancer-preventive effects. Cooked navy beans (whole beans), the insoluble fraction (bean residue) or soluble fraction of the 60% (vol:vol) ethanol extract of cooked navy beans (bean extract), or a modified AIN-93G diet (16.6% fat including 12.9% lard) as control diet were fed to 160 male obese ob/ob mice after 2 azoxymethane injections. In comparison to control-fed mice, dysplasia, adenomas, or adenocarcinomas were detected in fewer mice on either bean fraction diet (percent reduction from control: whole beans 54%, P = 0.10; bean residue 81%, P = 0.003; bean extract 91%, P = 0.007), and any type of colon lesions, including focal hyperplasia, were found in fewer mice on each of the 3 bean diets percent reduction from control: whole bean 56%, P = 0.04; bean residue 67%, P = 0.01; bean extract 87%, P = 0.0003. These results suggest that both the soluble and the insoluble fraction of the extract contribute to the cancer-protective effect of cooked navy beans.

Patulin surveillance in apple cider and juice marketed in Michigan.

Patulin is the most common mycotoxin found in apples and apple juices. The objective of this study was to determine the concentrations of patulin in (i) apple cider produced and marketed by Michigan apple cider mills during the fall seasons of 2002 to 2003 and 2003 to 2004 and (ii) apple juice and cider, including shelf-stable products, marketed in retail grocery stores in Michigan throughout 2005 and 2006. End product samples (n=493) obtained from 104 Michigan apple cider mills were analyzed for patulin concentration by using solid-phase extraction followed by high-performance liquid chromatography. Patulin was detected (> or =4 microg/liter) in 18.7% of all cider mill samples, with 11 samples (2.2%) having patulin concentrations of > or =50 microg/liter. A greater percentage of cider samples obtained from mills using thermal pasteurization contained detectable patulin (28.4%) than did those from mills using UV light radiation (13.5%) or no pathogen reduction treatment (17.0%). Among retail grocery store samples (n=159), 23% of apple juice and cider samples contained detectable patulin, with 18 samples (11.3%) having patulin concentrations of > or =50 microg/liter. The U.S. Food and Drug Administration (FDA) action level for patulin is 50 microg/kg. Some apple juice samples obtained from retail grocery stores had exceptionally high patulin concentrations, ranging up to 2700 microg/liter. Collectively, these results indicate that most apple cider and juice test samples from Michigan were below the FDA action level for patulin but that certain apple cider and juice processors have inadequate controls over patulin concentrations in final products. The industry, overall, should focus on improved quality of fruit used in juice production and improve culling procedures to reduce patulin concentrations.

High sucrose diets promote intestinal epithelial cell proliferation and tumorigenesis in APCMin mice by increasing insulin and IGF-I levels.

Epidemiological studies report that high sucrose consumption is associated with increased risk of colon cancer. One hypothesis is that this association is mediated by elevated circulatory insulin and IGF levels promoting intestinal proliferation. To test this hypothesis, APC Min mice and their wild type littermates were fed, starting at 4 wk of age, sucrose or cornstarch as the sole carbohydrate source in the absence or presence of low levels of dietary sulindac for 10 or 16 wk, respectively. APC Min mice fed sucrose had an increased tumor number in the proximal third of the small intestine in both studies and a higher incidence of papillary colon tumors in the 16-wk feeding study ( P ≤ 0.05). Mice fed sucrose (relative to cornstarch) had higher body weights and greater Ki67-labeling indexes in colonic epithelium than mice fed cornstarch in both feeding studies ( P ≤ 0.05). Furthermore, mice fed sucrose had higher serum glucose and liver IGF-I mRNA concentrations ( P ≤ 0.05) and tended to have higher serum insulin levels ( P = 0.08). These results support the hypothesis that high dietary sucrose intake promotes intestinal proliferation and tumorigenesis by increasing circulating levels of insulin and IGF-I.

Dietary carbohydrate source alters gene expression profile of intestinal epithelium in mice

High-sucrose consumption is associated with increased risk of human colon cancer. Our previous research indicated that high-sucrose diets (vs. cornstarch) promote intestinal epithelial cell proliferation and tumorigenesis as well as increase serum glucose and hepatic IGF-I mRNA levels in APC Min mice. To examine the role of functional pathways, in particular of IGF-I signaling, in sucrose-induced intestinal epithelial cell proliferation and tumorigenesis, we examined the effects of dietary carbohydrate source (sucrose vs. cornstarch) on gene expression in the intestinal epithelium using cDNA microarray and quantitative RT-PCR analysis. Dietary carbohydrate source significantly ( P < 0.05) altered mRNA expression of 109 known genes in the small intestinal epithelium, including many involved in metabolic pathways. Consumption of high-sucrose diets altered expression levels of genes involved in cell adhesion, cell cycle control, and transduction signaling, consistent with increased risk of intestinal tumorigenesis. High-sucrose intake also affected expression of genes involved in IGF-I signaling, including upregulating IGF-II and downregulating IGFBP3, which supports our hypothesis that IGF-I signaling could play a role in intestinal epithelial cell proliferation and tumorigenesis promoted by high-sucrose consumption.

Microbial levels in Michigan apple cider and their association with manufacturing practices

In recent decades, apple cider has been implicated in a series of outbreaks of foodborne illness. The objective of this study was to determine the presence and concentrations of pathogenic and indicator microorganisms in apple cider processed in Michigan and to evaluate the impact of thermal pasteurization, UV light radiation, and implementation of hazard analysis critical control point (HACCP) plans on these microbes. Cider samples were obtained from Michigan mills between 1997 and 2004 and analyzed for Escherichia coli O157:H7, Salmonella, generic E. coli, total coliforms, and aerobic bacteria. Neither E. coli O157:H7 nor Salmonella were detected in any tested cider samples, suggesting a very low frequency of pathogens in Michigan apple cider. The persistent and relatively high frequency of generic E. coli observed in samples obtained in all years indicates a continued risk of pathogen contamination in Michigan apple cider, especially when it is untreated. The use of thermal pasteurization or UV light radiation and reported implementation of HACCP plans were associated with lower frequency and counts of generic E. coli, total coliforms, and aerobic microorganisms. However, the relatively high counts of indicator organisms in some cider samples that were claimed to be treated according to these pathogen reduction measures indicates that some processors had inadequate practices, facilities, or equipment for pathogen reduction or did not consistently or adequately apply practices or pathogen-reduction equipment in an effective manner.