Determinants of blood acylcarnitine concentrations in healthy individuals of the European Prospective Investigation into Cancer and Nutrition

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  • Determinants

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  • Roland Wedekind
  • Joseph A. Rothwell
  • Vivian Viallon
  • Pekka Keski-Rahkonen
  • Julie A. Schmidt
  • Veronique Chajes
  • Vna Katzke
  • Theron Johnson
  • Maria Santucci de Magistris
  • Vittorio Krogh
  • Pilar Amiano
  • Carlotta Sacerdote
  • Daniel Redondo-Sánchez
  • José María Huerta
  • Pratik Pokharel
  • Paula Jakszyn
  • Rosario Tumino
  • Eva Ardanaz
  • Torkjel M. Sandanger
  • Anna Winkvist
  • Johan Hultdin
  • Matthias B. Schulze
  • Elisabete Weiderpass
  • Marc J. Gunter
  • Inge Huybrechts
  • Augustin Scalbert

Background & aims: Circulating levels of acylcarnitines (ACs) have been associated with the risk of various diseases such as cancer and type 2 diabetes. Diet and lifestyle factors have been shown to influence AC concentrations but a better understanding of their biological, lifestyle and metabolic determinants is needed. Methods: Circulating ACs were measured in blood by targeted (15 ACs) and untargeted metabolomics (50 ACs) in 7770 and 395 healthy participants of the European Prospective Investigation into Cancer and Nutrition (EPIC), respectively. Associations with biological and lifestyle characteristics, dietary patterns, self-reported intake of individual foods, estimated intake of carnitine and fatty acids, and fatty acids in plasma phospholipid fraction and amino acids in blood were assessed. Results: Age, sex and fasting status were associated with the largest proportion of AC variability (partial-r up to 0.19, 0.18 and 0.16, respectively). Some AC species of medium or long-chain fatty acid moiety were associated with the corresponding fatty acids in plasma (partial-r = 0.24) or with intake of specific foods such as dairy foods containing the same fatty acid. ACs of short-chain fatty acid moiety (propionylcarnitine and valerylcarnitine) were moderately associated with concentrations of branched-chain amino acids (partial-r = 0.5). Intake of most other foods and of carnitine showed little association with AC levels. Conclusions: Our results show that determinants of ACs in blood vary according to their fatty acid moiety, and that their concentrations are related to age, sex, diet, and fasting status. Knowledge on their potential determinants may help interpret associations of ACs with disease risk and inform on potential dietary and lifestyle factors that might be modified for disease prevention.

OriginalsprogEngelsk
TidsskriftClinical Nutrition
Vol/bind41
Udgave nummer8
Sider (fra-til)1735-1745
Antal sider11
ISSN0261-5614
DOI
StatusUdgivet - 2022

Bibliografisk note

Funding Information:
The national cohorts are supported by: Danish Cancer Society (Denmark); Ligue Contre le Cancer , Institut Gustave Roussy , Mutuelle Générale de l’Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France); German Cancer Aid , German Cancer Research Center ( DKFZ ), German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Federal Ministry of Education and Research ( BMBF ) (Germany); Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy, Compagnia di SanPaolo and National Research Council (Italy); Dutch Ministry of Public Health , Welfare and Sports ( VWS ), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund ( WCRF ), Statistics Netherlands (The Netherlands); Health Research Fund (FIS) - Instituto de Salud Carlos III ( ISCIII ), Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra, and the Catalan Institute of Oncology - ICO (Spain); Swedish Cancer Society , Swedish Research Council and County Councils of Skåne and Västerbotten (Sweden); Cancer Research UK (14136 to EPIC-Norfolk; C8221/A29017 to EPIC-Oxford), Medical Research Council (1000143 to EPIC-Norfolk; MR/M012190/1 to EPIC-Oxford) (United Kingdom). For the participants in the prostate cancer study, sample retrieval and preparation, and assays of metabolites were supported by Cancer Research UK (C8221/A19170), and funding for grant 2014/1183 was obtained from the World Cancer Research Fund ( WCRF UK ), as part of the World Cancer Research Fund International grant programme. We thank CERCA Programme/ Generalitat de Catalunya for institutional support.

Funding Information:
The coordination of EPIC is financially supported by International Agency for Research on Cancer ( IARC ) and also by the Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London which has additional infrastructure support provided by the NIHR Imperial Biomedical Research Centre ( BRC ).

Funding Information:
The coordination of EPIC is financially supported by International Agency for Research on Cancer (IARC) and also by the Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London which has additional infrastructure support provided by the NIHR Imperial Biomedical Research Centre (BRC).The national cohorts are supported by: Danish Cancer Society (Denmark); Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l'Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France); German Cancer Aid, German Cancer Research Center (DKFZ), German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Federal Ministry of Education and Research (BMBF) (Germany); Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy, Compagnia di SanPaolo and National Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands); Health Research Fund (FIS) - Instituto de Salud Carlos III (ISCIII), Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra, and the Catalan Institute of Oncology - ICO (Spain); Swedish Cancer Society, Swedish Research Council and County Councils of Skåne and Västerbotten (Sweden); Cancer Research UK (14136 to EPIC-Norfolk; C8221/A29017 to EPIC-Oxford), Medical Research Council (1000143 to EPIC-Norfolk; MR/M012190/1 to EPIC-Oxford) (United Kingdom). For the participants in the prostate cancer study, sample retrieval and preparation, and assays of metabolites were supported by Cancer Research UK (C8221/A19170), and funding for grant 2014/1183 was obtained from the World Cancer Research Fund (WCRF UK), as part of the World Cancer Research Fund International grant programme. We thank CERCA Programme/Generalitat de Catalunya for institutional support.

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© 2022

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