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

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 in-fluence AC concentrations but a better understanding of their biological, lifestyle and metabolic de-terminants 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. (c) 2022 Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND IGO license (http://creativecommons.org/licenses/by-nc-nd/3.0/igo/).

Automated summary

Circulating levels of acylcarnitines (ACs) are influenced by various factors such as age, sex, diet, and fasting status. Different types of ACs are associated with corresponding fatty acids in plasma, specific food intake, and concentrations of branched-chain amino acids. Understanding the determinants of ACs can help interpret their associations with disease risk and provide insights into potential dietary and lifestyle factors for disease prevention.