Associations of the 2018 World Cancer Research Fund/American Institute of Cancer Research (WCRF/AICR) cancer prevention recommendations with stages of colorectal carcinogenesis.

BACKGROUND: While adherence to cancer prevention recommendations is linked to lower risk of colorectal cancer (CRC), few have studied associations across the entire spectrum of colorectal carcinogenesis. Here, we studied the relationship of the standardized 2018 World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) Score for cancer prevention recommendations with detection of colorectal lesions in a screening setting. As a secondary objective, we examined to what extent the recommendations were being followed in an external cohort of CRC patients. METHODS: Adherence to the seven-point 2018 WCRF/AICR Score was measured in screening participants receiving a positive fecal immunochemical test and in CRC patients participating in an intervention study. Dietary intake, body fatness and physical activity were assessed using self-administered questionnaires. Multinomial logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for screen-detected lesions. RESULTS: Of 1486 screening participants, 548 were free from adenomas, 524 had non-advanced adenomas, 349 had advanced lesions and 65 had CRC. Adherence to the 2018 WCRF/AICR Score was inversely associated with advanced lesions; OR 0.82 (95% CI 0.71, 0.94) per score point, but not with CRC. Of the seven individual components included in the score, alcohol, and BMI seemed to be the most influential. Of the 430 CRC patients included in the external cohort, the greatest potential for lifestyle improvement was seen for the recommendations concerning alcohol and red and processed meat, where 10% and 2% fully adhered, respectively. CONCLUSIONS: Adherence to the 2018 WCRF/AICR Score was associated with lower probability of screen-detected advanced precancerous lesions, but not CRC. Although some components of the score seemed to be more influential than others (i.e., alcohol and BMI), taking a holistic approach to cancer prevention is likely the best way to prevent the occurrence of precancerous colorectal lesions.

Nutritional treatment is associated with longer survival in patients with pancreatic disease and concomitant risk of malnutrition.

BACKGROUND: Pancreatic diseases involve complex nutritional challenges. Despite this, conflicting evidence exists regarding the clinical relevance of detecting the risk of malnutrition and implementing systematic nutrition support for these patients. Thus, our aims were to investigate whether screening for malnutrition risk and initiating nutrition support are predictive of mortality for hospitalized patients with pancreatic diseases. DESIGN: From 2008 to 2018, 34 prevalence surveys of nutrition were conducted at Haukeland University Hospital (HUH), Norway. Risk of malnutrition was defined by a score of ≥3 in Nutritional Risk Screening 2002 (NRS 2002). Primary outcomes included overall, one-year, and one-month mortality, and were compared according to malnutrition risk and nutrition support for adult patients with ICD-10 codes of K85: acute pancreatitis, K86: other diseases of pancreas, and C25: malignant neoplasm of pancreas. Length of hospital stay (LOS) was included as a secondary outcome. RESULTS: Of the 283 patients investigated, risk of malnutrition was present in 61.5%. Risk of malnutrition was associated with higher overall mortality (Hazard Ratio (HR) = 1.67, 95% confidence interval (CI): 1.2-2.4, P = 0.003) and one-year mortality (HR = 1.89, 95% CI: 1.2-2.9, P = 0.004) compared to patients not at risk. Not receiving nutrition support for at-risk patients was associated with higher overall mortality (HR = 1.60, 95% CI: 1.1-2.4, P = 0.019) and one-year mortality (HR = 1.64, 95% CI: 1.04-2.6, P = 0.034) compared to patients at risk who received nutrition support. Patients at risk of malnutrition had increased LOS (20.5 nights vs 15.2 nights, P = 0.044) compared to patients not at risk of malnutrition. CONCLUSION: This study of hospitalized patients with pancreatic disease suggests that risk of malnutrition may be associated with higher mortality rates, whereas nutrition support may decrease mortality rates. CLINICAL TRIAL REGISTRY: Not registered.

Effects of using the MyFood decision support system on hospitalized patients' nutritional status and treatment: A randomized controlled trial.

BACKGROUND & AIMS: Compliance to guidelines for disease-related malnutrition is documented as poor. The practice of using paper-based dietary recording forms with manual calculation of the patient's nutritional intake is considered cumbersome, time-consuming and unfeasible among the nurses and does often not lead to appropriate nutritional treatment. We developed the digital decision support system MyFood to deliver a solution to these challenges. MyFood is comprised of an app for patients and a website for nurses and includes functions for dietary recording, evaluation of intake compared to requirements, and a report to nurses including tailored recommendations for nutritional treatment and a nutritional care plan for documentation. The study aimed to investigate the effects of using the MyFood decision support system during hospital stay on adult patients' nutritional status, treatment and hospital length of stay. The main outcome measure was weight change. METHODS: The study was a parallel-arm randomized controlled trial. Patients who were allocated to the intervention group used the MyFood app during their hospital stay and the nurses were encouraged to use the MyFood system. Patients who were allocated to the control group received routine care. RESULTS: We randomly assigned 100 patients (51.9 ± 14 y) to the intervention group (n = 49) and the control group (n = 51) between August 2018 and February 2019. Losses to follow-up were n = 5 in the intervention group and n = 1 in the control group. No difference was found between the two groups with regard to weight change. Malnutrition risk at discharge was present in 77% of the patients in the intervention group and 94% in the control group (p = 0.019). Nutritional treatment was documented for 81% of the patients in the intervention group and 57% in the control group (p = 0.011). A nutritional care plan was created for 70% of the intervention patients compared to 16% of the control patients (p < 0.001). CONCLUSIONS: The intervention had no effect on weight change during hospital stay. A higher proportion of the patients in the control group was malnourished or at risk of malnutrition at hospital discharge compared to the patients in the intervention group. The documentation of nutritional intake, treatment and nutritional care plans was higher for the patients using the MyFood system compared to the control group. This trial was registered at clinicaltrials.gov (NCT03412695).

Tomato-based randomized controlled trial in prostate cancer patients: Effect on PSA.

BACKGROUND & AIMS: The effect of lycopene-containing foods in prostate cancer development remains undetermined. We tested whether a lycopene-rich tomato intervention could reduce the levels of prostate specific antigen (PSA) in prostate cancer patients. METHODS: Prior to their curative treatment, 79 patients with prostate cancer were randomized to a nutritional intervention with either 1) tomato products containing 30 mg lycopene per day; 2) tomato products plus selenium, omega-3 fatty acids, soy isoflavones, grape/pomegranate juice, and green/black tea (tomato-plus); or 3) control diet for 3 weeks. RESULTS: The main analysis, which included patients in all risk categories, did not reveal differences in changes of PSA-values between the intervention and control groups. Post-hoc, exploratory analyses within intermediate risk (n = 41) patients based on tumor classification and Gleason score post-surgery, revealed that median PSA decreased significantly in the tomato group as compared to controls (-2.9% and +6.5% respectively, p = 0.016). In separate post-hoc analyses, we observed that median PSA-values decreased by 1% in patients with the highest increases in plasma lycopene, selenium and C20:5 n-3 fatty acid, compared to an 8.5% increase in the patients with the lowest increase in lycopene, selenium and C20:5 n-3 fatty acid (p = 0.003). Also, PSA decreased in patients with the highest increase in lycopene alone (p = 0.009). CONCLUSIONS: Three week nutritional interventions with tomato-products alone or in combination with selenium and n-3 fatty acids lower PSA in patients with non-metastatic prostate cancer. Our observation suggests that the effect may depend on both aggressiveness of the disease and the blood levels of lycopene, selenium and omega-3 fatty acids.

Coffee inhibits nuclear factor-kappa B in prostate cancer cells and xenografts.

Chronic inflammation contributes to prostate cancer and the transcription factor Nuclear Factor-kappa B (NF-κB) is constitutively active in most such cancers. We examine the effects of coffee on NF-κB and on the regulation of selected genes in human-derived prostate cancer cells (PC3) and in PC3 xenografts in athymic nude mice. PC3 cells stably transduced with an NF-κB-luciferase reporter were used both in vitro and for xenografts. NF-κB activity was measured by reporter assays, DNA binding and in vivo imaging. Gene expression was measured in PC3 cells, xenografts and tumor microenvironment by low-density arrays. Western blotting of activated caspases was used to quantify apoptosis. Coffee inhibited TNFα-induced NF-κB activity and DNA-binding in PC3 cells. Furthermore, coffee increased apoptosis and modulated expression of a number of inflammation- and cancer-related genes in TNFα-treated PC3 cells. In vivo imaging revealed a 31% lower NF-κB-luciferase activation in the xenografts of the mice receiving 5% coffee compared to control mice. Interestingly, we observed major changes in gene expression in the PC3 cells in xenografts as compared to PC3 cells in vitro. In PC3 xenografts, genes related to inflammation, apoptosis and cytoprotection were down-regulated in mice receiving coffee, and coffee also affected the gene expression in the xenograft microenvironment. Our data demonstrate that coffee inhibits NF-κB activity in PC3 cells in vitro and in xenografts. Furthermore, coffee modulates transcription of genes related to prostate cancer and inflammation. Our results are the first to suggest mechanistic links between coffee consumption and prostate cancer in an experimental mouse model.

Tomato paste alters NF-κB and cancer-related mRNA expression in prostate cancer cells, xenografts, and xenograft microenvironment.

Tomatoes may protect against prostate cancer development, possibly through targeting signaling pathways such as nuclear factor-κB (NF-κB). We investigated whether tomato paste could modulate NF-κB activity and cancer-related gene expression in human derived prostate cancer cells (PC3) and PC3 xenografts. PC3-cells were stably transduced with an NF-κB-luciferase construct, and treated with tomato extracts or vehicle control. Nude mice bearing PC3 xenografts were fed a Western-like diet with or without 10% tomato paste for 6.5 wk. The tomato diet significantly inhibited TNFα stimulated NF-κB activity in cultured PC3 cells, and modulated the expression of genes associated with inflammation, apoptosis, and cancer progression. Accumulation of lycopene occurred in liver, xenografts, and serum of mice fed tomato diet. Tomato paste in the diet did not affect tumor size in mice; however, there was a trend toward inhibition of NF-κB activity in the xenografts. The effect of tomato on gene expression was most prominent in the xenograft microenvironment, where among others NFKB2, STAT3, and STAT6 showed higher expression levels after tomato treatment. Our findings support biological activity of tomatoes in cancer-related inflammation.

Coffee and cancer risk, epidemiological evidence, and molecular mechanisms.

Although early studies suggested that coffee consumption might increase risk of some cancers, more comprehensive epidemiological and experimental data now generally indicate either neutral or beneficial effects. In this review, we summarize the current evidence for associations between breast, prostate, colorectal, and liver cancers and the consumption of coffee, and discuss the experimental evidence for potential chemopreventive mechanisms of coffee and coffee constituents. The epidemiological evidence consistently indicates that coffee protects against liver cancer, and also point toward protective effects for risk of colorectal cancers (with relative risks of 0.50 (95% CI: 0.42-0.59) and 0.83 (95% CI: 0.75-0.92), respectively, in the most recent meta-analyses). There seems to be no association between the overall risk of breast and prostate cancer and coffee intake. However, for subgroups such as postmenopausal breast cancers, advanced prostate cancers, and breast and prostate cancer survivors, an inverse association with coffee intake is indicated. Potential mechanisms for chemopreventive effects of coffee phytochemicals includes inhibition of oxidative stress and oxidative damage, regulation of DNA repair, phase II enzymatic activity, apoptosis, inflammation, as well as having antiproliferative, antiangiogenetic effects and antimetastatic effects. The experimental evidence for effects of coffee and coffee constituents on each of these processes is discussed.

Vitamin C and E supplementation hampers cellular adaptation to endurance training in humans: a double-blind, randomised, controlled trial.

In this double-blind, randomised, controlled trial, we investigated the effects of vitamin C and E supplementation on endurance training adaptations in humans. Fifty-four young men and women were randomly allocated to receive either 1000 mg of vitamin C and 235 mg of vitamin E or a placebo daily for 11 weeks. During supplementation, the participants completed an endurance training programme consisting of three to four sessions per week (primarily of running), divided into high-intensity interval sessions [4-6 × 4-6 min; >90% of maximal heart rate (HRmax)] and steady state continuous sessions (30-60 min; 70-90% of HRmax). Maximal oxygen uptake (VO2 max ), submaximal running and a 20 m shuttle run test were assessed and blood samples and muscle biopsies were collected, before and after the intervention. Participants in the vitamin C and E group increased their VO2 max (mean ± s.d.: 8 ± 5%) and performance in the 20 m shuttle test (10 ± 11%) to the same degree as those in the placebo group (mean ± s.d.: 8 ± 5% and 14 ± 17%, respectively). However, the mitochondrial marker cytochrome c oxidase subunit IV (COX4) and cytosolic peroxisome proliferator-activated receptor-γ coactivator 1 α (PGC-1α) increased in the m. vastus lateralis in the placebo group by 59 ± 97% and 19 ± 51%, respectively, but not in the vitamin C and E group (COX4: -13 ± 54%; PGC-1α: -13 ± 29%; P ≤ 0.03, between groups). Furthermore, mRNA levels of CDC42 and mitogen-activated protein kinase 1 (MAPK1) in the trained muscle were lower in the vitamin C and E group than in the placebo group (P ≤ 0.05). Daily vitamin C and E supplementation attenuated increases in markers of mitochondrial biogenesis following endurance training. However, no clear interactions were detected for improvements in VO2 max and running performance. Consequently, vitamin C and E supplementation hampered cellular adaptations in the exercised muscles, and although this did not translate to the performance tests applied in this study, we advocate caution when considering antioxidant supplementation combined with endurance exercise.

Plant extracts of spices and coffee synergistically dampen nuclear factor-κB in U937 cells.

A large array of bioactive plant compounds (phytochemicals) has been identified and synergy among these compounds might contribute to the beneficial effects of plant foods. The transcription factor nuclear factor-κB (NF-κB) has been suggested as a target for many phytochemicals. Due to the complexity of mechanisms involved in NF-κB regulation, including numerous feedback loops, and the large number of phytochemicals which regulate NF-κB activity, we hypothesize that synergistic or antagonistic effects are involved. The objectives of our study were to develop a statistical methodology to evaluate the concept of synergy and antagonism and to use this methodology in a monocytic cell line (U937 expressing an NF-κB-luciferase reporter) treated with lipopolysaccharide and phytochemical-rich plant extracts. Both synergistic and antagonistic effects were clearly observed. Observed synergy was most pronounced for the combinations of oregano and coffee, and thyme and oregano. For oregano and coffee the synergistic effect was highest at 5 mg/mL with 13.9% (P < .001), and for thyme and oregano the highest synergistic effects was at 3 mg/mL with 13.7% (P < .001). Dose dependent synergistic and antagonistic effects were observed for all combinations tested. In conclusion, this work presents a methodological tool to define synergy in experimental studies. Our results support the hypothesis that phytochemical-rich plants may exert synergistic and antagonistic effects on NF-κB regulation. Such complex mechanistic interactions between phytochemicals are likely to underlie the protective effects of a plant-based diet on life-style related diseases.

Coffee, broccoli and spices are strong inducers of electrophile response element-dependent transcription in vitro and in vivo - studies in electrophile response element transgenic mice.

SCOPE: Cytoprotective gene products, e.g. phase II - and antioxidant enzymes, are important in cellular redox homeostasis. A common feature of these genes is binding sites for transcription factor nuclear factor erythroid-2-related factor 2 (Nrf2), named electrophile response elements (EpREs) within their promoters. METHODS AND RESULTS: To identify dietary bioactive compounds and foods with Nrf2/EpRE inducing properties in an intact organism, we utilized transgenic mice encoding luciferase under control of EpRE from the thioredoxin promoter. We found that 18 of 31 phytochemicals and 10 of 14 dietary plant extracts induced EpRE activity in liver HepG2 cells. Surprisingly, some dietary plant extracts showed profound inducing capability as compared to pure compounds indicating combinatorial effects of compounds found in whole foods. Furthermore, intraperitoneal injections of carnosol, curcumin and tert benzohydroquinine induced EpRE-dependent promoter activity in transgenic mice. In further experiments with curcumin, we found highly induced EpRE activity in intestine, liver, kidney and spleen. Finally, a combination extract made of coffee, thyme, broccoli, rosemary, turmeric and red onion fed orally, induced EpRE mediated luciferase in lung and adipose tissue. CONCLUSION: These results show that plant-based foods contain compounds that can be absorbed and induce the antioxidant defence in a living organism in an organ-specific manner.

Extract of oregano, coffee, thyme, clove, and walnuts inhibits NF-kappaB in monocytes and in transgenic reporter mice.

The transcription factor NF-kappaB is a promising target for chemoprevention. Several dietary plants are efficient inhibitors of NF-kappaB activation in vitro and could act synergistically on the NF-kappaB signaling pathway. In this study, we tested whether dietary plant extracts could inhibit NF-kappaB activation in a synergistic manner in vitro. Second, we investigated the potency of the same dietary plant extracts in the inhibition of NF-kappaB activation in vivo. A combined extract of clove, oregano, thyme, walnuts, and coffee synergistically inhibited lipopolysaccaride (LPS)-induced NF-kappaB activation in a monocytic cell line, compared with the sum of effects from the single extracts. Transgenic NF-kappaB luciferase reporter mice were given a single dose of the combined extract and subsequently challenged with LPS. NF-kappaB activation was monitored by in vivo imaging for 6 hours. In addition, NF-kappaB activity in organs and the expression of immune-related genes in liver were investigated. Based on the area under the curve, the extract decreased whole body LPS-induced NF-kappaB activity the first 6 hours by 35% compared with control mice. Organ-specific NF-kappaB activation was inhibited in intestine, liver, testis, and epididymis of the mice receiving the combination extract. In addition, dietary plants reduced the expression of genes related to inflammation, cell migration, and proliferation in liver. This study shows that dietary plants may be potent modulators of NF-kappaB signaling both in vitro and in vivo, and thus support further investigation of consumption of these plant foods as part of a healthy diet or as a mode of chemoprevention.

Bilberry juice modulates plasma concentration of NF-kappaB related inflammatory markers in subjects at increased risk of CVD.

PURPOSE: Bilberries are abundant in polyphenols. Dietary polyphenols have been associated with strategies for prevention and treatment of chronic inflammatory diseases. We investigated the effect of bilberry juice on serum and plasma biomarkers of inflammation and antioxidant status in subjects with elevated levels of at least one risk factor for cardiovascular disease (CVD). METHODS: In a randomized controlled trial, participants consumed either bilberry juice (n = 31) or water (n = 31) for 4 weeks. RESULTS: Supplementation with bilberry juice resulted in significant decreases in plasma concentrations of C-reactive protein (CRP), interleukin (IL)-6, IL-15, and monokine induced by INF-gamma (MIG). Unexpectedly, an increase in the plasma concentration of tumor nuclear factor-alpha (TNF-alpha) was observed in the bilberry group. CRP, IL-6, IL15, MIG, and TNF-alpha are all target genes of nuclear factor- kappa B (NF-kappaB), -a transcription factor that is crucial in orchestrating inflammatory responses. Plasma quercetin and p-coumaric acid increased in the bilberry group, otherwise no differences were observed for clinical parameters, oxidative stress or antioxidant status. Furthermore, we studied the effect of polyphenols from bilberries on lipopolysaccharide (LPS)-induced NF-kappaB activation in a monocytic cell line. We observed that quercetin, epicatechin, and resveratrol inhibited NF-kappaB activation. CONCLUSIONS: These findings suggest that supplementation with bilberry polyphenols may modulate the inflammation processes. Further testing of bilberry supplementation as a potential strategy in prevention and treatment of chronic inflammatory diseases is warranted.

Degree of roasting is the main determinant of the effects of coffee on NF-kappaB and EpRE.

Coffee, one of the most popular beverages worldwide, is a major contributor of phytochemicals in the diet and contributes more than 50% of dietary antioxidants in many countries. A moderate intake of coffee has been linked to reduced risk of chronic diseases. Furthermore, experimental studies demonstrate bioactivity of coffee or coffee compounds in inflammation and oxidative stress, two major, related biological processes. We show that the degree of roasting correlates with the efficiency of dampening inflammation-induced NF-kappaB activity and inducing antioxidant defense through Nrf2/EpRE activity. Extracts of dark-roasted coffee inhibit NF-kappaB activity by more than 80% and induce EpRE activity more than 25-fold in vitro. In transgenic NF-kappaB-luciferase mice, a single dose of dark-roasted coffee extract per os inhibits NF-kappaB activation by 63% in the whole mouse, with the liver being the main target, with a 68% reduction in activity. In transgenic EpRE-luciferase mice, the extract of coffee increased overall EpRE activity by 30%, again with the liver as the main contributor, with a 2.7-fold increase. Our results demonstrate that dark-roasted coffee dampens a crucial mechanism in inflammation and induces a pivotal mechanism in oxidative stress defense.

Activation and inhibition of nuclear factor kappa B activity by cereal extracts: role of dietary phenolic acids.

The transcription factor nuclear factor kappa B (NF-kappaB) plays a critical role in stress, immune, and inflammatory responses, and the modulation of its activity can be a potentially effective preventive strategy for controlling certain diseases. Cereal grains contain phenolic compounds in concentrations comparable to those in fruits and vegetables, well-known for their beneficial effect on human health. In this study we aimed to examine the effect of different phenolic extracts from barley, oat, wheat, and buckwheat on the modulation of basal and lipopolysaccharide (LPS)-induced NF-kappaB activity and elucidate the role of phenolic acids in this modulation. Three extracts were prepared: extracts of free phenolic compounds (M1), extracts of free phenolic acids (M2), and extracts of bound phenolic acids (HY). Generally, extracts M2 showed the highest effect on modulation of NF-kappaB activity with strong inhibition of LPS-induced NF-kappaB activity at all concentrations and of the basal NF-kappaB activity at concentrations equal to or lower than 3 mg/mL. Most of extracts M1 and HY slightly increased both the basal and the LPS-induced NF-kappaB activation. However, at the highest concentrations (3 or 15 mg/mL) extracts HY inhibited LPS-induced NF-kappaB activation. Similar experiments with standard solutions of phenolic acids indicated their ability to modulate the NF-kappaB activity.

Anthocyanins inhibit nuclear factor-kappaB activation in monocytes and reduce plasma concentrations of pro-inflammatory mediators in healthy adults.

The transcription factor nuclear factor-kappaB (NF-kappaB) is activated by oxidative stress and pro-inflammatory stimuli and controls the expression of numerous genes involved in the inflammatory response. Dampening NF-kappaB activation and thereby limiting the inflammatory response have been suggested as a potential strategy to prevent chronic inflammatory diseases. In cultured monocytes, anthocyanins isolated from bilberries and black currants (Medox) efficiently suppressed LPS-induced activation of NF-kappaB. Furthermore, we studied the effect of anthocyanin supplementation (Medox, 300 mg/d for 3 wk) in a parallel-designed, placebo-controlled clinical trial (n = 120 men and women aged 40-74 y). Differences were observed in several NF-kappaB related inflammatory mediators in the Medox group compared to placebo. The changes in the NF-kappaB-controlled pro-inflammatory chemokines IL-8, "regulated upon activation, normal T cell expressed and secreted," (RANTES) and IFNalpha (an inducer of NF-kappaB activation) in the Medox group (45, 15, and 40% decreases from baseline, respectively) differed from those in the placebo group (20, 0, and 15% decreases from baseline, respectively) (P < 0.050). Similarly, changes in IL-4 and IL-13, 2 cytokines that mediate pro-inflammatory responses and induce NF-kappaB activation, in the Medox group (60 and 38% decreases from baseline, respectively) tended to differ from those in the placebo group (4 and 6% decreases) (P = 0.056 and, P = 0.089, respectively). These data suggest that anthocyanin supplementation may have a role in the prevention or treatment of chronic inflammatory diseases by inhibition of NF-kappaB transactivation and deceased plasma concentrations of pro-inflammatory chemokines, cytokines, and inflammatory mediators.

Modulation of pregnane X receptor- and electrophile responsive element-mediated gene expression by dietary polyphenolic compounds.

Based on animal models, dietary polyphenols are predicted to be promising chemopreventive agents in humans. Allspice, clove, and thyme extracts as well as defined dietary polyphenolic compounds were, therefore, tested for their ability to activate mechanisms related to phase 1 enzymes, i.e., the PXR-regulated CYP3A4 promoter, and phase 2 enzymes, i.e. the EpRE-regulated promoters of gastrointestinal glutathione peroxidase (GI-GPx) and heme oxygenase-1 (HO-1), examples of Nrf2-regulated genes. From the compounds tested, clove and thyme extracts as well as curcumin and resveratrol activated the PXR. PXR activation correlated with the activation of the CYP3A4 promoter in the case of thyme extract, curcumin, and resveratrol, but not in the case of clove extract. Allspice extract, EGCG, and quercetin did not activate PXR but enhanced CYP3A4 promoter activity. Thyme extract and quercetin activated the EpRE of HO-1. Both significantly activated the GI-GPx promoter, effects that depended on a functional EpRE. Resveratrol did not activate the isolated EpRE but enhanced the GI-GPx promoter activity, whereas clove extract even inhibited it. It is concluded that individual polyphenols as well as polyphenol-rich plant extracts may affect phase 1 and 2 enzyme expression by distinct mechanisms that must be elucidated, before potential health effects can reliably be predicted.