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5. Dietary flavonoid, lignan and antioxidant capacity and risk of hepatocellular carcinoma in the European prospective investigation into cancer and nutrition study

Author

Zamora-Ros, R, Fedirko, V, Trichopoulou, A, González, C, Bamia, C, Trepo, E, Nöthlings, U, Duarte-Salles, T, Serafini, M, Bredsdorff, L, Overvad, K, Tjønneland, A, Halkjaer, J, Fagherazzi, G, Perquier, F, Boutron-Ruault, M, Katzke, V, Lukanova, A, Floegel, A, Boeing, H, Lagiou, P, Trichopoulos, D, Saieva, C, Agnoli, C, and Mattiello, A

Abstract

Limited epidemiological evidence suggests a protective role for plant foods rich in flavonoids and antioxidants in hepatocellular cancer (HCC) etiology. Our aim was to prospectively investigate the association between dietary intake of flavonoids, lignans and nonenzymatic antioxidant capacity (NEAC) and HCC risk. Data from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort including 477,206 subjects (29.8% male) recruited from ten Western European countries, was analyzed. Flavonoid, lignan and NEAC intakes were calculated using a compilation of existing food composition databases linked to dietary information from validated dietary questionnaires. Dietary NEAC was based on ferric reducing antioxidant capacity (FRAP) and total radical-trapping antioxidant parameter (TRAP). Hepatitis B/C status was measured in a nested case-control subset. During a mean follow-up of 11-years, 191 incident HCC cases (66.5% men) were identified. Using Cox regression, multivariable adjusted models showed a borderline nonsignificant association of HCC with total flavonoid intake (highest versus lowest tertile, HR=0.65, 95% CI: 0.40-1.04; p=0.065), but not with lignans. Among flavonoid subclasses, flavanols were inversely associated with HCC risk (HR=0.62, 95% CI: 0.39-0.99; p=0.06). Dietary NEAC was inversely associated with HCC (FRAP: HR 0.50, 95% CI: 0.31-0.81; p=0.001; TRAP: HR 0.49, 95% CI: 0.31-0.79; p=0.002), but statistical significance was lost after exclusion of the first 2 years of follow-up. This study suggests that higher intake of dietary flavanols and antioxidants may be associated with a reduced HCC risk. What's new? Coffee, tea, fruits and vegetables, and certain other foods may protect against hepatocellular carcinoma (HCC), thanks to their antioxidant ingredients. This study lends fresh support to that idea, revealing specifically that dietary flavanols, which possess antioxidant activity, could play a favourable role in HCC prevention. Dietary antioxidant capacity from coffee intake in particular was found to be inversely associated with HCC risk, though statistical significance was lost after exclusion of the first two years of follow-up. Assessment of the bioavailability of flavonoids and other antioxidants is needed to confirm links between antioxidant intake and HCC risk. Department, Catalan Institute of Oncology, IDIBELL, Hospital Duran i Reynals, Gran Via 199-203, E-08908 L'Hospitalet de Llobregat, Barcelona, Spain. © 2013 UICC.

Published
2016
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6. Dietary intakes of individual flavanols and flavonols are inversely associated with incident type 2 diabetes in European populations

Author

Zamora-Ros, R, Forouhi, N, Sharp, S, González, C, Buijsse, B, Guevara, M, van der Schouw, Y, Amiano, P, Boeing, H, Bredsdorff, L, Fagherazzi, G, Feskens, E, Franks, P, Grioni, S, Katzke, V, Key, T, Khaw, K, Kühn, T, Masala, G, Mattiello, A, Molina-Montes, E, Nilsson, P, Overvad, K, Perquier, F, and Redondo, M

Abstract

Dietary flavanols and flavonols, flavonoid subclasses, have been recently associated with a lower risk of type 2 diabetes (T2D) in Europe. Even within the same subclass, flavonoids may differ considerably in bioavailability and bioactivity. We aimed to examine the association between individual flavanol and flavonol intakes and risk of developing T2D across European countries. The European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct case-cohort study was conducted in 8 European countries across 26 study centers with 340,234 participants contributing 3.99 million person-years of follow-up, among whom 12,403 incident T2D cases were ascertained and a center-stratified subcohort of 16,154 individuals was defined. We estimated flavonoid intake at baseline from validated dietary questionnaires using a database developed from Phenol-Explorer and USDA databases. We used country-specific Prentice-weighted Cox regression models and random-effects meta-analysis methods to estimate HRs. Among the flavanol subclass, we observed significant inverse trends between intakes of all individual flavan-3-ol monomers and risk of T2D in multivariable models (all P-trend < 0.05). We also observed significant trends for the intakes of proanthocyanidin dimers (HR for the highest vs. the lowest quintile: 0.81; 95% CI: 0.71, 0.92; P-trend = 0.003) and trimers (HR: 0.91; 95% CI: 0.80, 1.04; P-trend = 0.07) but not for proanthocyanidins with a greater polymerization degree. Among the flavonol subclass, myricetin (HR: 0.77; 95% CI: 0.64, 0.93; P-trend = 0.001) was associated with a lower incidence of T2D. This large and heterogeneous European study showed inverse associations between all individual flavan-3-ol monomers, proanthocyanidins with a low polymerization degree, and the flavonol myricetin and incident T2D. These results suggest that individual flavonoids have different roles in the etiology of T2D.

Published
2016

7. The association between dietary flavonoid and lignan intakes and incident type 2 diabetes in European populations: the EPIC-InterAct study

Author

Zamora-Ros, R, Forouhi, N, Sharp, S, González, C, Buijsse, B, Guevara, M, van der Schouw, Y, Amiano, P, Boeing, H, Bredsdorff, L, Clavel-Chapelon, F, Fagherazzi, G, Feskens, E, Franks, P, Grioni, S, Katzke, V, Key, T, Khaw, K, Kühn, T, Masala, G, Mattiello, A, Molina-Montes, E, Nilsson, P, Overvad, K, and Perquier, F

Abstract

OBJECTIVE: To study the association between dietary flavonoid and lignan intakes, and the risk of development of type 2 diabetes among European populations. RESEARCH DESIGN AND METHODS: The European Prospective Investigation into Cancer and Nutrition-InterAct case-cohort study included 12,403 incident type 2 diabetes cases and a stratified subcohort of 16,154 participants from among 340,234 participants with 3.99 million person-years of follow-up in eight European countries. At baseline, country-specific validated dietary questionnaires were used. A flavonoid and lignan food composition database was developed from the Phenol-Explorer, the U.K. Food Standards Agency, and the U.S. Department of Agriculture databases. Hazard ratios (HRs) from country-specific Prentice-weighted Cox regression models were pooled using random-effects meta-analysis. RESULTS: In multivariable models, a trend for an inverse association between total flavonoid intake and type 2 diabetes was observed (HR for the highest vs. the lowest quintile, 0.90 [95% CI 0.77-1.04]; P value trend = 0.040), but not with lignans (HR 0.88 [95% CI 0.72-1.07]; P value trend = 0.119). Among flavonoid subclasses, flavonols (HR 0.81 [95% CI 0.69-0.95]; P value trend = 0.020) and flavanols (HR 0.82 [95% CI 0.68-0.99]; P value trend = 0.012), including flavan-3-ol monomers (HR 0.73 [95% CI 0.57-0.93]; P value trend = 0.029), were associated with a significantly reduced hazard of diabetes. CONCLUSIONS: Prospective findings in this large European cohort demonstrate inverse associations between flavonoids, particularly flavanols and flavonols, and incident type 2 diabetes. This suggests a potential protective role of eating a diet rich in flavonoids, a dietary pattern based on plant-based foods, in the prevention of type 2 diabetes.

Published
2016

9. Critical review of methodology and application of risk ranking for prioritisation of food and feed related issues, on the basis of the size of anticipated health impact

Author

van der Fels-Klerx, H.J., van Asselt, E.D., Raley, M., Poulsen, M., Korsgaard, H., Bredsdorff, L., Nauta, M., Flari, V., D'Agostino, M., Coles, D.G., and Frewer, L.J.

Subjects
Marketing and Consumer Behaviour, BU Authenticiteit & Bioassays, BU Authenticity & Bioassays, Business Economics, Bedrijfseconomie, Life Science, WASS, Marktkunde en Consumentengedrag
Abstract

This study aimed to critically review methodologies for ranking of risks related to feed/food safety and nutritional hazards, on the basis of their anticipated human health impact. An extensive systematic literature review was performed to identify and characterize the available methodologies for risk ranking in the fields of feed and food safety and nutritional hazards, as well as the socio-economic field. Risk ranking methods from the environmental field were studied as well to determine whether approaches used in this field could also be applied for ranking human health risks related to feed and food safety and nutritional hazards. The review used a predefined search protocol. It covered the bibliographic databases Scopus, CAB Abstracts, Web of Sciences, and PubMed over the period 1993-2013. All references obtained were stored into an Endnote database and evaluated for their relevance. All references deemed to be relevant were studied in–depth so as to characterize the risk ranking method described. Characteristics of each method were stored in an Excel database. The methods for risk ranking were then grouped into method categories, which were described in general. These groups included: risk assessment, comparative risk assessment, risk ratio method, scoring method, cost of illness, DALY/QALY, willingness to pay, multi criteria decision analysis, risk matrix, flow charts/decision trees and expert judgment methods. Based on the characteristics of the individual methods and the method categories, an overarching framework was developed for selection of the appropriate method(s) that could be used for risk ranking of feed and food related hazards, on the basis of human health impact. This framework has the format of a decision tool, with which – given the characteristics of the risk ranking question at hand - the most appropriate method(s) can be selected. Application of this overall framework to several case studies showed it can be a useful tool for risk managers/assessors to select the most suitable method for risk ranking of feed/food and diet related hazards, on the basis of expected human health impact.

Published
2015

10. Critical review of methods for risk ranking of food related hazards, based on risks for human health.

Author

van der Fels-Klerx, H J, van Asselt, E D, Raley, M, Poulsen, M, Korsgaard, H, Bredsdorff, L, Nauta, M, D'Agostino, M, Coles, D, Marvin, H J P, Frewer, L J, van der Fels-Klerx, H J, van Asselt, E D, Raley, M, Poulsen, M, Korsgaard, H, Bredsdorff, L, Nauta, M, D'Agostino, M, Coles, D, Marvin, H J P, and Frewer, L J

Abstract

This study aimed to critically review methods for ranking risks related to food safety and dietary hazards on the basis of their anticipated human health impacts. A literature review was performed to identify and characterize methods for risk ranking from the fields of food, environmental science and socio-economic sciences. The review used a predefined search protocol, and covered the bibliographic databases Scopus, CAB Abstracts, Web of Sciences, and PubMed over the period 1993-2013. All references deemed relevant, on the basis of of predefined evaluation criteria, were included in the review, and the risk ranking method characterized. The methods were then clustered - based on their characteristics - into eleven method categories. These categories included: risk assessment, comparative risk assessment, risk ratio method, scoring method, cost of illness, health adjusted life years, multi-criteria decision analysis, risk matrix, flow charts/decision trees, stated preference techniques and expert synthesis. Method categories were described by their characteristics, weaknesses and strengths, data resources, and fields of applications. It was concluded there is no single best method for risk ranking. The method to be used should be selected on the basis of risk manager/assessor requirements, data availability, and the characteristics of the method. Recommendations for future use and application are provided.

Published
2016

11. Dietary intakes of individual flavanols and flavonols are inversely associated with incident type 2 diabetes in European populations

Author

Zamora Ros, R, Forouhi, Ng, Sharp, Sj, González, Ca, Buijsse, B, Guevara, M, van der Schouw YT, Amiano, P, Boeing, H, Bredsdorff, L, Fagherazzi, G, Feskens, Ej, Franks, Pw, Grioni, S, Katzke, V, Key, Tj, Khaw, Kt, Kühn, T, Masala, G, Mattiello, A, Molina Montes, E, Nilsson, Pm, Overvad, K, Perquier, F, Redondo, Ml, Ricceri, Fulvio, Rolandsson, O, Romieu, I, Roswall, N, Scalbert, A, Schulze, M, Slimani, N, Spijkerman, Am, Tjonneland, A, Tormo, Mj, Touillaud, M, Tumino, R, van der A., Dl, van Woudenbergh GJ, Langenberg, C, Riboli, E, Wareham, Nj, Forouhi, Nita [0000-0002-5041-248X], Sharp, Stephen [0000-0003-2375-1440], Khaw, Kay-Tee [0000-0002-8802-2903], Langenberg, Claudia [0000-0002-5017-7344], Wareham, Nicholas [0000-0003-1422-2993], and Apollo - University of Cambridge Repository

Subjects
Adult, Male, Flavonols, Nutritional Status, Motor Activity, White People, Risk Factors, Surveys and Questionnaires, Humans, Nutritional Epidemiology, Proanthocyanidins, Prospective Studies, Life Style, Proportional Hazards Models, Flavonoids, Nutrition and Dietetics, Incidence, Middle Aged, Diet, Europe, Näringslära, Diabetes Mellitus, Type 2, Socioeconomic Factors, Multivariate Analysis, Female, Follow-Up Studies
Abstract

Dietary flavanols and flavonols, flavonoid subclasses, have been recently associated with a lower risk of type 2 diabetes (T2D) in Europe. Even within the same subclass, flavonoids may differ considerably in bioavailability and bioactivity. We aimed to examine the association between individual flavanol and flavonol intakes and risk of developing T2D across European countries. The European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct case-cohort study was conducted in 8 European countries across 26 study centers with 340,234 participants contributing 3.99 million person-years of follow-up, among whom 12,403 incident T2D cases were ascertained and a center-stratified subcohort of 16,154 individuals was defined. We estimated flavonoid intake at baseline from validated dietary questionnaires using a database developed from Phenol-Explorer and USDA databases. We used country-specific Prentice-weighted Cox regression models and random-effects meta-analysis methods to estimate HRs. Among the flavanol subclass, we observed significant inverse trends between intakes of all individual flavan-3-ol monomers and risk of T2D in multivariable models (all P-trend < 0.05). We also observed significant trends for the intakes of proanthocyanidin dimers (HR for the highest vs. the lowest quintile. 0.81; 95% Cl: 0.71, 0.92; P-trend = 0.003) and trimers (HR: 0.91; 95% Cl: 0.80, 1.04; P-trend = 0.07) but not for proanthocyanidins with a greater polymerization degree. Among the flavonol subclass, myricetin (HR: 0.77; 95% Cl: 0.64, 0.93; P-trend = 0.001) was associated with a lower incidence of T2D. This large and heterogeneous European study showed inverse associations between all individual flavan-3-ol monomers, proanthocyanidins with a low polymerization degree, and the flavonol myricetin and incident T2D. These results suggest that individual flavonoids have different roles in the etiology of T2D.

Published
2014
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12. Dietary flavonoid, lignan and antioxidant capacity and risk of hepatocellular carcinoma in the European prospective investigation into cancer and nutrition study

Author

Zamora-Ros, R, González, CA, Fedirko, V, Duarte-Salles, T, Jenab, M, Trichopoulou, A, Bamia, C, Lagiou, P, Trichopoulos, D, Trepo, E, Nöthlings, U, Serafini, M, Bredsdorff, L, Overvad, K, Tjønneland, A, Halkjær, J, Fagherazzi, G, Perquier, F, Boutron-Ruault, M-C, Katzke, V, Lukanova, A, Floegel, A, Boeing, H, Saieva, C, Agnoli, C, Mattiello, A, Tumino, R, Sacerdote, C, Bas Bueno-de-Mesquita, H, Peeters, PH, Riboli, E, Weiderpass, E, Engeset, D, Skeie, G, Vicente Argüelles, M, Molina-Montes, E, Dorronsoro, M, José Tormo, M, Ardanaz, E, Ericson, U, Sonestedt, E, Sund, M, Landberg, R, Khaw, K-T, Wareham, NJ, and Crowe, FL

Subjects
Flavonoids, Male, Risk, Carcinoma, Hepatocellular, Liver Neoplasms, Nutritional Status, Feeding Behavior, Middle Aged, Risk Assessment, Antioxidants, Lignans, Diet, Cohort Studies, Europe, Risk Factors, Case-Control Studies, Surveys and Questionnaires, Humans, Female, Prospective Studies, Follow-Up Studies
Abstract

Limited epidemiological evidence suggests a protective role for plant foods rich in flavonoids and antioxidants in hepatocellular cancer (HCC) etiology. Our aim was to prospectively investigate the association between dietary intake of flavonoids, lignans and nonenzymatic antioxidant capacity (NEAC) and HCC risk. Data from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort including 477,206 subjects (29.8% male) recruited from ten Western European countries, was analyzed. Flavonoid, lignan and NEAC intakes were calculated using a compilation of existing food composition databases linked to dietary information from validated dietary questionnaires. Dietary NEAC was based on ferric reducing antioxidant capacity (FRAP) and total radical-trapping antioxidant parameter (TRAP). Hepatitis B/C status was measured in a nested case-control subset. During a mean follow-up of 11-years, 191 incident HCC cases (66.5% men) were identified. Using Cox regression, multivariable adjusted models showed a borderline nonsignificant association of HCC with total flavonoid intake (highest versus lowest tertile, HR=0.65, 95% CI: 0.40-1.04; p=0.065), but not with lignans. Among flavonoid subclasses, flavanols were inversely associated with HCC risk (HR=0.62, 95% CI: 0.39-0.99; p=0.06). Dietary NEAC was inversely associated with HCC (FRAP: HR 0.50, 95% CI: 0.31-0.81; p=0.001; TRAP: HR 0.49, 95% CI: 0.31-0.79; p=0.002), but statistical significance was lost after exclusion of the first 2 years of follow-up. This study suggests that higher intake of dietary flavanols and antioxidants may be associated with a reduced HCC risk. What's new? Coffee, tea, fruits and vegetables, and certain other foods may protect against hepatocellular carcinoma (HCC), thanks to their antioxidant ingredients. This study lends fresh support to that idea, revealing specifically that dietary flavanols, which possess antioxidant activity, could play a favourable role in HCC prevention. Dietary antioxidant capacity from coffee intake in particular was found to be inversely associated with HCC risk, though statistical significance was lost after exclusion of the first two years of follow-up. Assessment of the bioavailability of flavonoids and other antioxidants is needed to confirm links between antioxidant intake and HCC risk. Department, Catalan Institute of Oncology, IDIBELL, Hospital Duran i Reynals, Gran Via 199-203, E-08908 L'Hospitalet de Llobregat, Barcelona, Spain. © 2013 UICC.

Published
2013
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13. The association between dietary flavonoid and lignan intakes and incident type 2 diabetes in European populations: the EPIC-InterAct study

Author

Zamora-Ros, R, Forouhi, NG, Sharp, SJ, González, CA, Buijsse, B, Guevara, M, van der Schouw, YT, Amiano, P, Boeing, H, Bredsdorff, L, Clavel-Chapelon, F, Fagherazzi, G, Feskens, EJ, Franks, PW, Grioni, S, Katzke, V, Key, TJ, Khaw, KT, Kühn, T, Masala, G, Mattiello, A, Molina-Montes, E, Nilsson, PM, Overvad, K, Perquier, F, Quirós, JR, Romieu, I, Sacerdote, C, Scalbert, A, Schulze, M, Slimani, N, Spijkerman, AM, Tjonneland, A, Tormo, MJ, Tumino, R, van der A, DL, Langenberg, C, Riboli, E, and Wareham, NJ

Subjects
Flavonoids, Male, Incidence, Nutritional Status, Feeding Behavior, Middle Aged, Lignans, Europe, Diabetes Mellitus, Type 2, Population Surveillance, Humans, Female, Prospective Studies, Epidemiology/Health Services Research, Follow-Up Studies, Original Research
Abstract

OBJECTIVE: To study the association between dietary flavonoid and lignan intakes, and the risk of development of type 2 diabetes among European populations. RESEARCH DESIGN AND METHODS: The European Prospective Investigation into Cancer and Nutrition-InterAct case-cohort study included 12,403 incident type 2 diabetes cases and a stratified subcohort of 16,154 participants from among 340,234 participants with 3.99 million person-years of follow-up in eight European countries. At baseline, country-specific validated dietary questionnaires were used. A flavonoid and lignan food composition database was developed from the Phenol-Explorer, the U.K. Food Standards Agency, and the U.S. Department of Agriculture databases. Hazard ratios (HRs) from country-specific Prentice-weighted Cox regression models were pooled using random-effects meta-analysis. RESULTS: In multivariable models, a trend for an inverse association between total flavonoid intake and type 2 diabetes was observed (HR for the highest vs. the lowest quintile, 0.90 [95% CI 0.77-1.04]; P value trend = 0.040), but not with lignans (HR 0.88 [95% CI 0.72-1.07]; P value trend = 0.119). Among flavonoid subclasses, flavonols (HR 0.81 [95% CI 0.69-0.95]; P value trend = 0.020) and flavanols (HR 0.82 [95% CI 0.68-0.99]; P value trend = 0.012), including flavan-3-ol monomers (HR 0.73 [95% CI 0.57-0.93]; P value trend = 0.029), were associated with a significantly reduced hazard of diabetes. CONCLUSIONS: Prospective findings in this large European cohort demonstrate inverse associations between flavonoids, particularly flavanols and flavonols, and incident type 2 diabetes. This suggests a potential protective role of eating a diet rich in flavonoids, a dietary pattern based on plant-based foods, in the prevention of type 2 diabetes.

Published
2013
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14. Critical review of methods for risk ranking of food-related hazards, based on risks for human health.

Author

Van der Fels-Klerx, H. J., Van Asselt, E. D., Raley, M., Poulsen, M., Korsgaard, H., Bredsdorff, L., Nauta, M., D'agostino, M., Coles, D., Marvin, H. J. P., and Frewer, L. J.

Subjects
FOOD safety, HEALTH risk assessment, HAZARDS, HEALTH impact assessment, ENVIRONMENTAL sciences
Abstract

This study aimed to critically review methods for ranking risks related to food safety and dietary hazards on the basis of their anticipated human health impacts. A literature review was performed to identify and characterize methods for risk ranking from the fields of food, environmental science and socio-economic sciences. The review used a predefined search protocol, and covered the bibliographic databases Scopus, CAB Abstracts, Web of Sciences, and PubMed over the period 1993-2013. All references deemed relevant, on the basis of predefined evaluation criteria, were included in the review, and the risk ranking method characterized. The methods were then clustered-based on their characteristics-into eleven method categories. These categories included: risk assessment, comparative risk assessment, risk ratio method, scoring method, cost of illness, health adjusted life years (HALY), multi-criteria decision analysis, risk matrix, flow charts/decision trees, stated preference techniques and expert synthesis. Method categories were described by their characteristics, weaknesses and strengths, data resources, and fields of applications. It was concluded there is no single best method for risk ranking. The method to be used should be selected on the basis of risk manager/assessor requirements, data availability, and the characteristics of the method. Recommendations for future use and application are provided. [ABSTRACT FROM AUTHOR]

Published
2018
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15. Critical review of methodology and application of risk ranking for prioritisation of food and feed related issues, on the basis of the size of anticipated health impact

Author

van der Fels‐Klerx, H.J., primary, van Asselt, E.D., additional, Raley, M., additional, Poulsen, M., additional, Korsgaard, H., additional, Bredsdorff, L., additional, Nauta, M., additional, Flari, V., additional, d'Agostino, M., additional, Coles, D., additional, and Frewer, L., additional

Published
2015
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17. Dietary Flavonoid Intake and Esophageal Cancer Risk in the European Prospective Investigation into Cancer and Nutrition Cohort

Author

Vermeulen, E., primary, Zamora-Ros, R., additional, Duell, E. J., additional, Lujan-Barroso, L., additional, Boeing, H., additional, Aleksandrova, K., additional, Bueno-de-Mesquita, H. B., additional, Scalbert, A., additional, Romieu, I., additional, Fedirko, V., additional, Touillaud, M., additional, Fagherazzi, G., additional, Perquier, F., additional, Molina-Montes, E., additional, Chirlaque, M.-D., additional, Vicente Arguelles, M., additional, Amiano, P., additional, Barricarte, A., additional, Pala, V., additional, Mattiello, A., additional, Saieva, C., additional, Tumino, R., additional, Ricceri, F., additional, Trichopoulou, A., additional, Vasilopoulou, E., additional, Ziara, G., additional, Crowe, F. L., additional, Khaw, K.-T., additional, Wareham, N. J., additional, Lukanova, A., additional, Grote, V. A., additional, Tjonneland, A., additional, Halkjaer, J., additional, Bredsdorff, L., additional, Overvad, K., additional, Siersema, P. D., additional, Peeters, P. H. M., additional, May, A. M., additional, Weiderpass, E., additional, Skeie, G., additional, Hjartaker, A., additional, Landberg, R., additional, Johansson, I., additional, Sonestedt, E., additional, Ericson, U., additional, Riboli, E., additional, and Gonzalez, C. A., additional

Published
2013
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19. Chemical Mixture Calculator - A novel tool for mixture risk assessment.

Author

Boberg J, Bredsdorff L, Petersen A, Löbl N, Jensen BH, Vinggaard AM, and Nielsen E

Subjects
Databases, Chemical, Humans, Internet, No-Observed-Adverse-Effect Level, Phthalic Acids toxicity, Risk Assessment, Complex Mixtures toxicity, Software
Abstract

Humans are continuously exposed to complex chemical mixtures from foods and the environment. Experimental models in vivo and in vitro have increased our knowledge on how we can predict mixture effects. To accommodate a need for tools for efficient mixture risk assessment across different chemical classes and exposure sources, we have developed fit-for-purpose criteria for grouping of chemicals and a web-based tool for mixture risk assessment. The Chemical Mixture Calculator (available at www.chemicalmixturecalculator.dk) can be used for mixture risk assessment or identification of main drivers of risk. The underlying database includes hazard and exposure estimates for more than 200 chemicals in foods and environment. We present a range of cumulative assessment groups for effects on haematological system, kidney, liver, nervous system, developmental and reproductive system, and thyroid. These cumulative assessment groups are useful for grouping of chemicals at several levels of refinement depending on the question addressed. We present a mixture risk assessment case for phthalates, evaluated with and without contributions from other chemicals with similar effects. This case study shows the usefulness of the tool as a starting point for mixture risk assessment by the risk assessor, and emphasizes that solid scientific insight regarding underlying assumptions and uncertainties is crucial for result interpretation., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Published
2021
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20. The impact of dietary habits on contaminant exposures.

Author

Petersen A, Jensen BH, Löbl NM, Nielsen E, Bredsdorff L, Fagt S, Christensen T, and Boberg J

Subjects
Adolescent, Adult, Aged, Child, Child, Preschool, Denmark, Environmental Pollutants analysis, Female, Humans, Male, Middle Aged, Risk Assessment, Young Adult, Dietary Exposure, Environmental Pollutants toxicity, Feeding Behavior, Food Contamination analysis
Abstract

This study shows that dietary habits have an impact on contaminant exposures. A tool was developed to calculate chemical exposures for different Danish population groups. First, the tool divided the individuals into quartiles using a previously developed scoring system for how well their diet complies with the Danish dietary guidelines. Then the exposure was calculated for several contaminants for both children and adults within the quartiles. Comparisons were then performed between the exposures for the lowest and highest quartiles. The individuals having a diet more in compliance with the dietary guidelines have a higher exposure to contaminants than individuals having a diet less in compliance with the dietary guidelines. Standard deviations for the mean exposure were in general large indicating that the consumption patterns can be very different within each population group. A risk characterisation for each contaminant and population group was performed by calculation of Hazard Quotients (HQs). For dioxins and dioxin-like polychlorinated biphenyls (PCDD/F + DL-PCBs), inorganic arsenic, and lead all HQs were above 1 indicating a potential risk for all groups. For hexabromocyclododecane (HBCDD) and nickel, a potential risk was identified for at least one group. For all other contaminants the HQs were well below 1 for all groups., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Published
2020
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22. Are wild and cultivated flowers served in restaurants or sold by local producers in Denmark safe for the consumer?

Author

Egebjerg MM, Olesen PT, Eriksen FD, Ravn-Haren G, Bredsdorff L, and Pilegaard K

Subjects
Animals, Denmark, Flowers chemistry, Humans, Plants, Edible chemistry, Flowers toxicity, Food Safety, Plants, Edible toxicity, Restaurants
Abstract

New Nordic Food has within the last decade received much media coverage with chefs of top restaurants using wild plants for foods. As part of a control campaign, the Danish Veterinary and Food Administration visited 150 restaurants and local food producers from May-October 2016 and investigated their use of plants picked from the wild, cultivated in private gardens or market gardens. Among the species used were the flowers from 23 plants. Here we present a safety evaluation of these flowers based on published phytochemical investigations and toxicological data in humans, farm animals, pets, or experimental animals. Of the 23 flowers reviewed, nine contained compounds with toxic or potentially toxic effects if eaten, two contained unidentified toxic compound(s), and four were flowers from plants with potentially toxic compounds present in other plant parts or related species. Many of the flowers may be considered novel, since a use to a significant degree in Europe prior to 15 May 1997 before Regulation (EC) 258/97 on novel food and novel food ingredients came into force could not be established. In conclusion, this review illuminates a striking lack of chemical and toxicological data of many of the proposed wild or cultivated flowers for food use., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Published
2018
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23. Raspberry ketone in food supplements--High intake, few toxicity data--A cause for safety concern?

Author

Bredsdorff L, Wedebye EB, Nikolov NG, Hallas-Møller T, and Pilegaard K

Subjects
Animals, Flavoring Agents toxicity, No-Observed-Adverse-Effect Level, Quantitative Structure-Activity Relationship, Rats, Safety, Butanones toxicity, Dietary Supplements analysis, Dietary Supplements toxicity
Abstract

Raspberry ketone (4-(4-hydroxyphenyl)-2-butanone) is marketed on the Internet as a food supplement. The recommended intake is between 100 and 1400 mg per day. The substance is naturally occurring in raspberries (up to 4.3 mg/kg) and is used as a flavouring substance. Toxicological studies on raspberry ketone are limited to acute and subchronic studies in rats. When the lowest recommended daily dose of raspberry ketone (100 mg) as a food supplement is consumed, it is 56 times the established threshold of toxicological concern (TTC) of 1800 μg/day for Class 1 substances. The margin of safety (MOS) based on a NOAEL of 280 mg/kg bw/day for lower weight gain in rats is 165 at 100 mg and 12 at 1400 mg. The recommended doses are a concern taking into account the TTC and MOS. Investigations of raspberry ketone in quantitative structure-activity relationship (QSAR) models indicated potential cardiotoxic effects and potential effects on reproduction/development. Taking into account the high intake via supplements, the compound's toxic potential should be clarified with further experimental studies. In UK the pure compound is regarded as novel food requiring authorisation prior to marketing but raspberry ketone is not withdrawn from Internet sites from this country., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Published
2015
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24. Urinary flavonoid excretion and risk of acute coronary syndrome in a nested case-control study.

Author

Bredsdorff L, Obel T, Dethlefsen C, Tjønneland A, Schmidt EB, Rasmussen SE, and Overvad K

Subjects
Case-Control Studies, Chromatography, Liquid, Denmark, Diet, Female, Humans, Incidence, Isoflavones administration & dosage, Isoflavones urine, Kaempferols administration & dosage, Kaempferols urine, Life Style, Logistic Models, Male, Mass Spectrometry, Middle Aged, Risk Factors, Acute Coronary Syndrome prevention & control, Flavonoids administration & dosage, Flavonoids urine
Abstract

Background: Epidemiologic studies have suggested that a higher intake of flavonoids may be associated with lower risk of ischemic heart disease. However, the traditional estimation of flavonoid intake by using dietary assessment methods is affected by subjective measures., Objective: We examined whether the objective measurement of dietary flavonoids excreted in urine is associated with lower risk of acute coronary syndrome (ACS)., Design: A case-control study was nested in the Danish Diet, Cancer and Health cohort study. Cases were identified in participants who had received a first-time ACS diagnosis in the Danish National Patient Registry after the time of enrollment into the Diet, Cancer and Health study. The excretion of 10 flavonoids, which represent 5 subclasses, was measured in spot urine samples by using liquid chromatography-mass spectrometry., Results: A total of 393 eligible cases with ACS were identified and matched to 393 noncases by using incidence density sampling. For kaempferol, most of the individual ORs were statistically significant and from 42% to 61% lower when the higher 4 quintiles were compared with the lowest quintile. The P-trend was not significant. For daidzein, individual ORs were 5-38% lower. None of the individual ORs were significant, but the P-trend was 0.041. For the remaining flavonoids, there were no significant relations between urinary excretion and risk of ACS., Conclusions: Except for kaempferol and daidzein, there were no significant associations between the urinary excretion of flavonoids and risk of ACS. A lack of relations may be a result of the use of short-term exposure measures.

Published
2013
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25. Dietary flavonoid and lignan intake and breast cancer risk according to menopause and hormone receptor status in the European Prospective Investigation into Cancer and Nutrition (EPIC) Study.

Author

Zamora-Ros R, Ferrari P, González CA, Tjønneland A, Olsen A, Bredsdorff L, Overvad K, Touillaud M, Perquier F, Fagherazzi G, Lukanova A, Tikk K, Aleksandrova K, Boeing H, Trichopoulou A, Trichopoulos D, Dilis V, Masala G, Sieri S, Mattiello A, Tumino R, Ricceri F, Bueno-de-Mesquita HB, Peeters PH, Weiderpass E, Skeie G, Engeset D, Menéndez V, Travier N, Molina-Montes E, Amiano P, Chirlaque MD, Barricarte A, Wallström P, Sonestedt E, Sund M, Landberg R, Khaw KT, Wareham NJ, Travis RC, Scalbert A, Ward HA, Riboli E, and Romieu I

Subjects
Adult, Aged, Breast Neoplasms etiology, Breast Neoplasms metabolism, Female, Humans, Incidence, Middle Aged, Postmenopause, Premenopause, Receptors, Estrogen, Receptors, Progesterone, Risk Factors, Surveys and Questionnaires, Breast Neoplasms epidemiology, Diet, Flavonoids, Lignans
Abstract

Evidence on the association between dietary flavonoids and lignans and breast cancer (BC) risk is inconclusive, with the possible exception of isoflavones in Asian countries. Therefore, we investigated prospectively dietary total and subclasses of flavonoid and lignan intake and BC risk according to menopause and hormonal receptor status in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. The study included 334,850 women, mostly aged between 35 and 70 years from ten European countries. At baseline, country-specific validated dietary questionnaires were used. A flavonoid and lignan food composition database was developed from the US Department of Agriculture, the Phenol-Explorer and the UK Food Standards Agency databases. Cox regression models were used to analyse the association between dietary flavonoid/lignan intake and the risk of developing BC. During an average 11.5-year follow-up, 11,576 incident BC cases were identified. No association was observed between the intake of total flavonoids [hazard ratio comparing fifth to first quintile (HRQ5-Q1) 0.97, 95 % confidence interval (CI): 0.90-1.04; P trend = 0.591], isoflavones (HRQ5-Q1 1.00, 95 % CI: 0.91-1.10; P trend = 0.734), or total lignans (HRQ5-Q1 1.02, 95 % CI: 0.93-1.11; P trend = 0.469) and overall BC risk. The stratification of the results by menopausal status at recruitment or the differentiation of BC cases according to oestrogen and progesterone receptors did not affect the results. This study shows no associations between flavonoid and lignan intake and BC risk, overall or after taking into account menopausal status and BC hormone receptors.

Published
2013
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26. Differences in dietary intakes, food sources and determinants of total flavonoids between Mediterranean and non-Mediterranean countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) study.

Author

Zamora-Ros R, Knaze V, Luján-Barroso L, Romieu I, Scalbert A, Slimani N, Hjartåker A, Engeset D, Skeie G, Overvad K, Bredsdorff L, Tjønneland A, Halkjær J, Key TJ, Khaw KT, Mulligan AA, Winkvist A, Johansson I, Bueno-de-Mesquita HB, Peeters PH, Wallström P, Ericson U, Pala V, de Magistris MS, Polidoro S, Tumino R, Trichopoulou A, Dilis V, Katsoulis M, Huerta JM, Martínez V, Sánchez MJ, Ardanaz E, Amiano P, Teucher B, Grote V, Bendinelli B, Boeing H, Förster J, Touillaud M, Perquier F, Fagherazzi G, Gallo V, Riboli E, and González CA

Subjects
Adult, Aged, Diet, Mediterranean, Europe, Female, Food Analysis, Fruit, Humans, Male, Mediterranean Region, Middle Aged, Tea, Wine, Diet, Flavonoids classification
Abstract

A greater adherence to the traditional Mediterranean (MED) diet is associated with a reduced risk of developing chronic diseases. This dietary pattern is based on higher consumption of plant products that are rich in flavonoids. We compared the total flavonoid dietary intakes, their food sources and various lifestyle factors between MED and non-MED countries participating in the EPIC study. Flavonoid intakes and their food sources for 35,628 subjects, aged 35-74 years and recruited between 1992 and 2000, in twenty-six study centres were estimated using standardised 24 h dietary recall software (EPIC-Soft®). An ad hoc food composition database on flavonoids was compiled using analytical data from the United States Department of Agriculture and Phenol-Explorer databases. Moreover, it was expanded to include using recipes, estimations of missing values and flavonoid retention factors. No significant differences in total flavonoid mean intake between non-MED countries (373·7 mg/d) and MED countries (370·2 mg/d) were observed. In the non-MED region, the main contributors were proanthocyanidins (48·2%) and flavan-3-ol monomers (24·9%) and the principal food sources were tea (25·7%) and fruits (32·8%). In the MED region, proanthocyanidins (59·0%) were by far the most abundant contributor and fruits (55·1%), wines (16·7%) and tea (6·8%) were the main food sources. The present study shows similar results for total dietary flavonoid intakes, but significant differences in flavonoid class intakes, food sources and some characteristics between MED and non-MED countries. These differences should be considered in studies about the relationships between flavonoid intake and chronic diseases.

Published
2013
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27. Dietary flavonoid and lignan intake and gastric adenocarcinoma risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study.

Author

Zamora-Ros R, Agudo A, Luján-Barroso L, Romieu I, Ferrari P, Knaze V, Bueno-de-Mesquita HB, Leenders M, Travis RC, Navarro C, Sánchez-Cantalejo E, Slimani N, Scalbert A, Fedirko V, Hjartåker A, Engeset D, Skeie G, Boeing H, Förster J, Li K, Teucher B, Agnoli C, Tumino R, Mattiello A, Saieva C, Johansson I, Stenling R, Redondo ML, Wallström P, Ericson U, Khaw KT, Mulligan AA, Trichopoulou A, Dilis V, Katsoulis M, Peeters PH, Igali L, Tjønneland A, Halkjær J, Touillaud M, Perquier F, Fagherazzi G, Amiano P, Ardanaz E, Bredsdorff L, Overvad K, Ricceri F, Riboli E, and González CA

Subjects
Adenocarcinoma epidemiology, Adenocarcinoma etiology, Adult, Aged, Anticarcinogenic Agents therapeutic use, Cohort Studies, Europe epidemiology, Female, Flavonoids therapeutic use, Follow-Up Studies, Humans, Incidence, Life Style, Lignans therapeutic use, Male, Middle Aged, Prospective Studies, Risk, Sex Factors, Stomach Neoplasms epidemiology, Stomach Neoplasms etiology, Adenocarcinoma prevention & control, Anticarcinogenic Agents administration & dosage, Diet adverse effects, Flavonoids administration & dosage, Lignans administration & dosage, Stomach Neoplasms prevention & control
Abstract

Background: Several experimental studies have suggested potential anticarcinogenic effects of flavonoids, although epidemiologic evidence for the impact of dietary flavonoids on risk of gastric cancer (GC) is limited., Objective: We investigated the association between intake of dietary flavonoids and lignans and incident GC., Design: The study followed 477,312 subjects (29.8% men) aged 35-70 y from 10 European countries who participated in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Validated dietary questionnaires and lifestyle information were collected at baseline. A food-composition database on flavonoids and lignans was compiled by using data from USDA and Phenol-Explorer databases., Results: During an average follow-up of 11 y, 683 incident GC cases (57.8% men) were mostly validated by a panel of pathologists and used in this analysis. We observed a significant inverse association between total flavonoid intake and GC risk in women (HR: 0.81; 95% CI: 0.70, 0.94; for the continuous variable after log₂ transformation) but not in men (HR: 0.97; 95% CI: 0.85, 1.09). In women, significant inverse associations with GC risk were also observed for intakes of some flavonoid subgroups (anthocyanidins, flavonols, flavones, and flavanols), particularly with intestinal type tumors for total flavonoid and flavanol intakes (P-heterogeneity < 0.1). After stratification by smoking status and sex, there was no significant heterogeneity in these associations between ever- and never-smokers., Conclusion: Total dietary flavonoid intake is associated with a significant reduction in the risk of GC in women.

Published
2012
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