To study the effect of NAS in humans, we examined the relationship between long-term NAS consumption (based on a validated food frequency questionnaire, see Methods) and various clinical parameters in data collected from 381 non-diabetic individuals (44% males and 56% females; age 43.3 6 13.2) in an ongoing clinical nutritional study. We found significant positive correlations between NAS consumption and several metabolic-syndrome-related clinical parameters (Supplementary Table 6), including increased weight and waist-to-hip ratio (measures of central obesity); higherfasting blood glucose, glycosylated haemoglobin (HbA1C%) and glucose tolerance test (GTT, measures of impaired glucose tolerance), and elevated serum alanine aminotransferase (ALT, measure of hepatic damage that is likely to be secondary, in this context, to non-alcoholicfatty liver disease).Moreover, the levels of glycosylated haemoglobin (HbA1C%), indicative of glucose concentration over the previous 3 months, were significantly increased when comparing a subgroup of high NAS consumers (40 individuals) to nonNAS consumers (236 individuals, Fig. 4a, rank sum P , 0.002).
