Introduction

Dietary interventions have been suggested as a tool to improve cardiometabolic health to decrease the risk for type 2 diabetes, coronary artery disease (CAD), stroke and mortality.1 2 Randomised dietary intervention studies with hard outcomes are, however, challenging and there is controversy as to which dietary qualities would promote cardiometabolic health the most3 even though several ‘healthy/prudent’ data-driven dietary patterns have been found to associate with lower risk of cardiometabolic disease in observational prospective studies.4 Understanding the molecular events resulting from dietary intakes, and their relationship to disease and health outcomes would facilitate future intervention studies through identification of diet-modifiable metabolic pathways and disease mechanisms.

Metabolomics can be used to measure how the levels of circulating metabolites are connected to dietary intakes. A large number of metabolites in the human circulation derive directly from the digestion and metabolism of food components and constitute the food metabolome.5 Both endogenous plasma metabolites and metabolites from the food metabolome have been shown to correlate with certain dietary patterns estimated using questionnaires on dietary intake in cohort studies,6 and with certain food items in randomised controlled feeding trials.7 The connection between diet and the metabolome is particularly interesting because circulating levels of specific metabolites have previously been shown to predict future risk of type 2 diabetes,8 CAD9 and premature mortality.10 By combining data from dietary intake, metabolomics and clinical outcomes, certain metabolites could be identified as associated with both a healthy diet and cardiometabolic health, thus pinpointing potential mechanisms of action of diet at the molecular level and candidate substances for future interventions by randomised controlled trials aiming to improve cardiometabolic health.11

Here, we measured fasting plasma levels of 112 metabolites from the baseline examination of a Swedish population-based prospective cohort study, the Malmö Diet and Cancer study, comprising 3236 individuals without cardiovascular disease (CVD) and type 2 diabetes at study entry. We first assessed these metabolites’ association with a previously identified health conscious food pattern (HCFP) which was associated with protection from CVD and type 2 diabetes.12 Thereafter, HCFP-associated metabolites were related to incidence of type 2 diabetes, CVD, cardiovascular and overall mortality during a median follow-up time of 21 years. Our aim was to identify metabolites connected to both the HCFP and to protection from cardiometabolic disease in order to highlight metabolic pathways and mechanisms linking healthy dietary intake to cardiometabolic health.