Plasma metabolomics of children with aberrant serum lipids and inadequate micronutrient intake

Blood lipids have served as key biomarkers for cardiovascular disease (CVD) risk, yet emerging evidence indicates metabolite profiling might reveal a larger repertoire of small molecules that reflect altered metabolism, and which may be associated with early disease risk. Inadequate micronutrient status may also drive or exacerbate CVD risk factors that emerge during childhood. This study aimed to understand relationships between serum lipid levels, the plasma metabolome, and micronutrient status in 38 children (10 ± 0.8 years) at risk for CVD. Serum lipid levels were measured via autoanalyzer and average daily micronutrient intakes were calculated from 3-day food logs. Plasma metabolites were extracted using 80% methanol and analyzed via ultra-high-performance liquid chromatography-tandem mass spectrometry. Spearman's rank-order coefficients (rs) were computed for correlations between the following serum lipids [total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and triglycerides (TG)], 805 plasma metabolites, and 17 essential micronutrients. Serum lipid levels in the children ranged from 128-255 mg/dL for total cholesterol, 67-198 mg/dL for LDL, 31-58 mg/dL for HDL, and 46-197 mg/dL for TG. The majority of children (71 to 100%) had levels lower than the Recommended Daily Allowance for vitamin E, calcium, magnesium, folate, vitamin D, and potassium. For sodium, 76% of children had levels above the Upper Limit of intake. Approximately 30% of the plasma metabolome (235 metabolites) were significantly correlated with serum lipids. As expected, plasma cholesterol was positively correlated with serum total cholesterol (rs = 0.6654; p<0.0001). Additionally, 27 plasma metabolites were strongly correlated with serum TG (rs ≥0.60; p≤0.0001), including alanine and diacylglycerols, which have previously been associated with cardiometabolic and atherosclerotic risk in adults and experimental animals. Plasma metabolite profiling alongside known modifiable risk factors for children merit continued investigation in epidemiological studies to assist with early CVD detection, mitigation, and prevention via lifestyle-based interventions.