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1. Food additive emulsifiers and cancer risk: Results from the French prospective NutriNet-Santé cohort.

Author

Laury Sellem, Bernard Srour, Guillaume Javaux, Eloi Chazelas, Benoit Chassaing, Emilie Viennois, Charlotte Debras, Nathalie Druesne-Pecollo, Younes Esseddik, Fabien Szabo de Edelenyi, Nathalie Arnault, Cédric Agaësse, Alexandre De Sa, Rebecca Lutchia, Inge Huybrechts, Augustin Scalbert, Fabrice Pierre, Xavier Coumoul, Chantal Julia, Emmanuelle Kesse-Guyot, Benjamin Allès, Pilar Galan, Serge Hercberg, Mélanie Deschasaux-Tanguy, and Mathilde Touvier

Subjects
Medicine
Abstract

BackgroundEmulsifiers are widely used food additives in industrially processed foods to improve texture and enhance shelf-life. Experimental research suggests deleterious effects of emulsifiers on the intestinal microbiota and the metabolome, leading to chronic inflammation and increasing susceptibility to carcinogenesis. However, human epidemiological evidence investigating their association with cancer is nonexistent. This study aimed to assess associations between food additive emulsifiers and cancer risk in a large population-based prospective cohort.Methods and findingsThis study included 92,000 adults of the French NutriNet-Santé cohort without prevalent cancer at enrolment (44.5 y [SD: 14.5], 78.8% female, 2009 to 2021). They were followed for an average of 6.7 years [SD: 2.2]. Food additive emulsifier intakes were estimated for participants who provided at least 3 repeated 24-h dietary records linked to comprehensive, brand-specific food composition databases on food additives. Multivariable Cox regressions were conducted to estimate associations between emulsifiers and cancer incidence. Overall, 2,604 incident cancer cases were diagnosed during follow-up (including 750 breast, 322 prostate, and 207 colorectal cancers). Higher intakes of mono- and diglycerides of fatty acids (FAs) (E471) were associated with higher risks of overall cancer (HR high vs. low category = 1.15; 95% CI [1.04, 1.27], p-trend = 0.01), breast cancer (HR = 1.24; 95% CI [1.03, 1.51], p-trend = 0.04), and prostate cancer (HR = 1.46; 95% CI [1.09, 1.97], p-trend = 0.02). In addition, associations with breast cancer risk were observed for higher intakes of total carrageenans (E407 and E407a) (HR = 1.32; 95% CI [1.09, 1.60], p-trend = 0.009) and carrageenan (E407) (HR = 1.28; 95% CI [1.06, 1.56], p-trend = 0.01). No association was detected between any of the emulsifiers and colorectal cancer risk. Several associations with other emulsifiers were observed but were not robust throughout sensitivity analyses. Main limitations include possible exposure measurement errors in emulsifiers intake and potential residual confounding linked to the observational design.ConclusionsIn this large prospective cohort, we observed associations between higher intakes of carrageenans and mono- and diglycerides of fatty acids with overall, breast and prostate cancer risk. These results need replication in other populations. They provide new epidemiological evidence on the role of emulsifiers in cancer risk.Trial registrationClinicalTrials.gov NCT03335644.

Published
2024
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2. Dietary exposure to nitrites and nitrates in association with type 2 diabetes risk: Results from the NutriNet-Santé population-based cohort study.

Author

Bernard Srour, Eloi Chazelas, Nathalie Druesne-Pecollo, Younes Esseddik, Fabien Szabo de Edelenyi, Cédric Agaësse, Alexandre De Sa, Rebecca Lutchia, Charlotte Debras, Laury Sellem, Inge Huybrechts, Chantal Julia, Emmanuelle Kesse-Guyot, Benjamin Allès, Pilar Galan, Serge Hercberg, Fabrice Pierre, Mélanie Deschasaux-Tanguy, and Mathilde Touvier

Subjects
Medicine
Abstract

BackgroundNitrites and nitrates occur naturally in water and soil and are commonly ingested from drinking water and dietary sources. They are also used as food additives, mainly in processed meats, to increase shelf life and to avoid bacterial growth. Experimental studies suggested both benefits and harmful effects of nitrites and nitrates exposure on type 2 diabetes (T2D) onset, but epidemiological and clinical data are lacking. We aimed to study these associations in a large population-based prospective cohort study, distinguishing foods and water-originated nitrites/nitrates from those from food additives.Methods and findingsOverall, 104,168 adults from the French NutriNet-Santé cohort study (2009 to 2021, 79.1% female, mean age [SD] = 42.7 [14.5]) were included. Associations between self-reported exposure to nitrites and nitrates (evaluated using repeated 24-h dietary records, linked to a comprehensive food composition database and accounting for commercial names/brands details of industrial products) and risk of T2D were assessed using cause-specific multivariable Cox proportional hazard models adjusted for known risk factors (sociodemographic, anthropometric, lifestyle, medical history, and nutritional factors). During a median follow-up duration of 7.3 years (interquartile range: [3.2; 10.1] years), 969 incident T2D cases were ascertained. Total nitrites and foods and water-originated nitrites were both positively associated with a higher T2D risk (HRtertile 3 vs.1 = 1.27 (95% CI 1.04 to 1.54), Ptrend = 0.009 and 1.26 (95% CI 1.03 to 1.54), Ptrend = 0.02, respectively). Participants with higher exposure to additives-originated nitrites (i.e., above the sex-specific median) and specifically those having higher exposure to sodium nitrite (e250) had a higher T2D risk compared with those who were not exposed to additives-originated nitrites (HR higher consumers vs. non-consumers = 1.53 (95% CI 1.24 to 1.88), Ptrend < 0.001 and 1.54 (95% CI 1.26 to 1.90), Ptrend < 0.001, respectively). There was no evidence for an association between total, foods and water-originated, or additives-originated nitrates and T2D risk (all Ptrend = 0.7). No causal link can be established from this observational study. Main limitations include possible exposure measurement errors and the lack of validation versus specific nitrites/nitrates biomarkers; potential selection bias linked to the healthier behaviors of the cohort's participants compared to the general population; potential residual confounding linked to the observational design, as well as a self-reported, yet cross-checked, case ascertainment.ConclusionsThe findings of this large prospective cohort did not support any potential benefits for dietary nitrites and nitrates. They suggested that a higher exposure to both foods and water-originated and additives-originated nitrites was associated with higher T2D risk in the NutriNet-Santé cohort. This study provides a new piece of evidence in the context of current debates about updating regulations to limit the use of nitrites as food additives. The results need to be replicated in other populations.Trial registrationClinicalTrials.gov NCT03335644 (https://clinicaltrials.gov/ct2/show/NCT03335644).

Published
2023
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3. Dairy as a Source of Iodine and Protein in the UK: Implications for Human Health Across the Life Course, and Future Policy and Research

Author

Oliver C. Witard, Sarah C. Bath, Mariana Dineva, Laury Sellem, Ana-Isabel Mulet-Cabero, Laura H. van Dongen, Ju-Sheng Zheng, Carina Valenzuela, and Benoit Smeuninx

Subjects
dairy, iodine, protein, pregnancy, sarcopenia, Nutrition. Foods and food supply, TX341-641
Abstract

This narrative review summarizes key concepts in dairy nutrition for supporting human health throughout the life course. Milk and dairy products have been a staple component of our diet for thousands of years and provide a wide range of important nutrients that are otherwise difficult to obtain from dairy-free diets. In this review, we provide a broad perspective on the nutritional roles of iodine and dairy protein in supporting human health during pregnancy and early life, childhood and adolescence, mid- and later-life. New methodologies to identify biomarkers of dairy intake via high-throughput mass spectrometry are discussed, and new concepts such as the role of the food matrix in dairy nutrition are introduced. Finally, future policy and research related to the consumption of dairy and non-dairy alternatives for health are discussed with a view to improving nutritional status across the lifespan.

Published
2022
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4. Deep Lipidomics in Human Plasma: Cardiometabolic Disease Risk and Effect of Dietary Fat Modulation

Author

Fabian Eichelmann, Laury Sellem, Clemens Wittenbecher, Susanne Jäger, Olga Kuxhaus, Marcela Prada, Rafael Cuadrat, Kim G. Jackson, Julie A. Lovegrove, and Matthias B. Schulze

Subjects
Adult, Fatty Acids, Myocardial Infarction, Middle Aged, Dietary Fats, Cohort Studies, Diabetes Mellitus, Type 2, Physiology (medical), Lipidomics, Humans, Prospective Studies, Cardiology and Cardiovascular Medicine, epidemiology, cardiovascular diseases, diet, food, and nutrition, lipids, diabetes mellitus, type 2, cholesterol, Aged
Abstract

Background: In blood and tissues, dietary and endogenously generated fatty acids (FAs) occur in free form or as part of complex lipid molecules that collectively represent the lipidome of the respective tissue. We assessed associations of plasma lipids derived from high-resolution lipidomics with incident cardiometabolic diseases and subsequently tested if the identified risk-associated lipids were sensitive to dietary fat modification. Methods: The EPIC Potsdam cohort study (European Prospective Investigation into Cancer and Nutrition) comprises 27 548 participants recruited within an age range of 35 to 65 years from the general population around Potsdam, Germany. We generated 2 disease-specific case cohorts on the basis of a fixed random subsample (n=1262) and all respective cohort-wide identified incident primary cardiovascular disease (composite of fatal and nonfatal myocardial infarction and stroke; n=551) and type 2 diabetes (n=775) cases. We estimated the associations of baseline plasma concentrations of 282 class-specific FA abundances (calculated from 940 distinct molecular species across 15 lipid classes) with the outcomes in multivariable-adjusted Cox models. We tested the effect of an isoenergetic dietary fat modification on risk-associated lipids in the DIVAS randomized controlled trial (Dietary Intervention and Vascular Function; n=113). Participants consumed either a diet rich in saturated FAs (control), monounsaturated FAs, or a mixture of monounsaturated and n-6 polyunsaturated FAs for 16 weeks. Results: Sixty-nine lipids associated (false discovery rate Conclusions: We identified several lipids associated with cardiometabolic disease risk. A subset was beneficially altered by a dietary fat intervention that supports the substitution of dietary saturated FAs with unsaturated FAs as a potential tool for primary disease prevention.

Published
2022

5. Association between a pro plant-based dietary score and cancer risk in the prospective NutriNet-santé cohort

Author

Abou, Kane-Diallo, Bernard, Srour, Laury, Sellem, Mélanie, Deschasaux, Paule, Latino-Martel, Serge, Hercberg, Pilar, Galan, Philippine, Fassier, Françoise, Guéraud, Fabrice H, Pierre, Emmanuelle, Kesse-Guyot, Benjamin, Allès, Mathilde, Touvier, Equipe 3: EREN- Equipe de Recherche en Epidémiologie Nutritionnelle (CRESS - U1153), Université Paris 13 (UP13)-Institut National de la Recherche Agronomique (INRA)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Prévention et promotion de la cancérogénèse par les aliments (ToxAlim-PPCA), ToxAlim (ToxAlim), Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Ministère de la Santé, Institut de Veille Sanitaire (InVS), Institut National de la Prévention et de l’Education pour la Santé (INPES), Région Ile-de-France (CORDDIM), Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Recherche Agronomique (INRA), Conservatoire National des Arts et Métiers (CNAM), French National Cancer Institute [INCa_8085] (Université Paris 13), PhD grants from the Canceropôle Ile de France/Région Ile de France (public funding), Srour, Bernard, Université Paris 13 (UP13)-Institut National de la Recherche Agronomique (INRA)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA), and Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)

Subjects
Male, Meat, [SDV]Life Sciences [q-bio], Middle Aged, Prognosis, dietary score, Diet, Survival Rate, [SDV] Life Sciences [q-bio], Diabetes Mellitus, Type 2, animal foods, Cardiovascular Diseases, Risk Factors, Fruit, Neoplasms, Vegetables, Humans, cancer, Female, Prospective Studies, pro plant-based dietary score, Follow-Up Studies, prospective study
Abstract

International audience; Diverse plant products (e.g. fruits, vegetables, legumes) are associated with decreased cancer risk at several locations while red and processed meat were found to increase cancer risk. A pro plant-based dietary score reflecting the relative contribution of consumed plant vs animal products was developed, and was associated with lower overall mortality, type 2 diabetes and cardiovascular disease risk, among omnivorous adults. For the first time, we investigated the prospective associations between this pro plant-based dietary score and cancer risk. This study included 42,544 men and women of the French NutriNet-Santé prospective cohort (2009-2016) aged ≥45 years who completed at least three 24-hr-dietary records during the first year of follow-up. The risk of developing cancer was compared across sex-specific tertiles of pro plant-based dietary score by multivariable Cox models. In total, 1,591 first primary incident cancer cases were diagnosed during follow-up, among which 487 breast, 243 prostate, 198 digestive and 68 lung cancers. A higher pro plant-based dietary score was associated with decreased risks of overall (HRt3vs.t1 =0.85; 95% CI 0.76, 0.97; Ptrend =0.02), digestive (HRt3vs.t1 =0.68; 95% CI 0.47; 0.99; Ptrend = 0.04) and lung (HRt3vs.t1 =0.47; 95% CI 0.25, 0.90; Ptrend =0.02) cancer, though no substantial associations were found for breast or prostate cancers. This large cohort study supports a beneficial role of higher intakes of plant-based products along with lower intakes of animal products, within a balanced omnivorous diet, regarding primary cancer prevention. These results are consistent with mechanistic evidence from experimental studies.

Published
2018

6. Cancer-Specific and General Nutritional Scores and Cancer Risk: Results from the Prospective NutriNet-Santé Cohort

Author

Mathilde Touvier, Laury Sellem, Moufidath Adjibade, Philippine Fassier, Serge Hercberg, Bernard Srour, Mélanie Deschasaux, Paule Latino-Martel, Emmanuelle Kesse-Guyot, Thibault Fiolet, Céline Lavalette, Equipe 3: EREN- Equipe de Recherche en Epidémiologie Nutritionnelle (CRESS - U1153), Université Paris 13 (UP13)-Institut National de la Recherche Agronomique (INRA)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital avicenne, Hôpital Avicenne-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Sorbonne Paris Nord, The NutriNet-Sante study was supported by the following public institutions: Ministere de la Santé, Institut de Veille Sanitaire (InVS), Institut National de la Prévention et de l'Education pour la Santé (INPES), Région Ile-de-France (CORDDIM), Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Recherche Agronomique (INRA), Conservatoire National des Arts et Métiers (CNAM), and Université Paris 13. Philippine Fassier was funded by a PhD grant from the Cancéropole Ile de France/Région Ile de France (public funding). Moufidath Adjibade was funded by a PhD grant from Paris 13 University (public funding). Bernard Srour was funded by the French National Cancer Institute (grant number INCa_8085)., Institut National de la Recherche Agronomique (INRA)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Paris 13 (UP13)-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Srour, Bernard, Université Paris 13 (UP13)-Institut National de la Recherche Agronomique (INRA)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), and HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153))

Subjects
Male, Cancer Research, medicine.medical_specialty, Colorectal cancer, [SDV]Life Sciences [q-bio], Population, Nutritional Status, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Internal medicine, medicine, Humans, 030212 general & internal medicine, Prospective Studies, Risk factor, education, Prospective cohort study, Life Style, Proportional Hazards Models, 2. Zero hunger, education.field_of_study, Cancer prevention, business.industry, Incidence, Cancer, Middle Aged, medicine.disease, United States, 3. Good health, Diet, [SDV] Life Sciences [q-bio], Oncology, 030220 oncology & carcinogenesis, Case-Control Studies, Cohort, Female, business, Colorectal Neoplasms, Cohort study
Abstract

Several national and international authorities have proposed nutritional and lifestyle recommendations with the aim of improving health of the general population. Scores of adherence to these recommendations can be calculated at the individual level. Here, we investigated the associations between four nutritional scores and overall, breast, prostate, and colorectal cancer risk in a large prospective population-based cohort: the cancer-specific World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) score, the Alternate Healthy Eating Index 2010 (AHEI-2010), a score based on adherence to the Mediterranean diet (MEDI-LITE), and the French National Nutrition Health Program-Guideline Score (PNNS-GS). This study included 41,543 participants aged ≥40 years from the NutriNet-Santé cohort (2009–2017). A total of 1,489 overall incident cancers were diagnosed. A one-point increment of the WCRF/AICR score was significantly associated with decreased overall [12%; 95% confidence interval (CI), 8%–16%; P < 0.0001], breast (14%; 95% CI, 6%–21%; P = 0.001), and prostate (12%; 95% CI, 0%–22%; P = 0.05) cancer risks. Hazard ratio for colorectal cancer risk was 0.86 (95% CI, 0.72–1.03; P = 0.09). The PNNS-GS score was associated with reduced colorectal cancer risk (P = 0.04) and AHEI-2010 was associated with reduced overall cancer risk (P = 0.03). The WCRF/AICR score performed best. Compared with other tested scores, it included a stronger penalty for alcohol, which is a major risk factor for several cancer sites. Better adherence to nutritional recommendations, especially those designed for cancer prevention, could substantially contribute to decreased cancer incidence. Significance: This large prospective population-based cohort study suggests that following dietary recommendations such as the ones proposed by the World Cancer Research Fund/American Institute for Cancer Research could significantly contribute to cancer prevention. Cancer Res; 78(15); 4427–35. ©2018 AACR.

Published
2018

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