Association of plasma nitrite levels with obesity and metabolic syndrome in the Old Order Amish.

Objectives: Plasma nitrite is a metabolite of nitric oxide and reflects endogenous nitric oxide synthase (NOS) activity. Although plasma nitrites were previously linked with obesity and metabolic syndrome (MetS), the direction of association remains inconsistent, possibly due to sample heterogeneity. In a relatively homogeneous population, we hypothesized that nitrite levels will be positively associated with overweight/obesity and MetS.

Methods: Fasting nitrite levels were measured in 116 Old Order Amish (78% women). We performed age-and-sex-adjusted ancovas to compare nitrite levels between three groups (a) overweight/obese(-)MetS(-), (b) overweight/obese(+)MetS(-) and (c) overweight/obese(+)MetS)(+). Multivariate linear regressions were conducted on nitrite associations with continuous metabolic variables, with successive adjustments for demographics, body mass index, C-reactive protein and neopterin.

Results: Nitrite levels were higher in the obese/overweight(+)MetS(+) group than in the other two groups ( p  < 0.001). Nitrites were positively associated with levels of triglycerides ( p  < 0.0001), total cholesterol ( p  = 0.048), high-density lipoprotein/cholesterol ratio ( p  < 0.0001) and fasting glucose ( p  < 0.0001), and negatively correlated with high-density lipoprotein-cholesterol ( p  < 0.0001). These associations were robust to adjustments for body mass index and inflammatory markers.

Conclusion: Further investigation of the connection between obesity/MetS and plasma nitrite levels may lead to novel dietary and pharmacological approaches that ultimately may contribute to reducing the increasing burden of obesity, MetS and cardiovascular morbidity and mortality.